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Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level. Subcutaneous (inguinal) and visceral (epididymal) adipocytes were isolated from C57BL/6J mice fed either chow or high-fat diet. Cell size was determined using coulter counter method, glucose uptake and cytosolic volume were assessed using glucose tracer assays. Total and GLUT4 protein content expressions were determined by Western blot. We found that basal glucose uptake per cell was preserved independent of diet or fat depot origin. Insulin-stimulated glucose uptake per cell was sustained in visceral adipocytes but decreased with adipose expansion in subcutaneous adipocytes. In parallel, the cytosolic space and total protein increased proportionally to total cellular volumetric expansion in visceral, but not in subcutaneous, adipocytes, whereas GLUT4 content decreased exclusively in expanding subcutaneous adipocytes. Together, these data support the existence of distinct phenotypic adipocyte traits that could limit cellular insulin responsiveness. Potentially, these characteristics account for fat depot-specific differences related to glucose transport capacity. NEW & NOTEWORTHY This work illustrates that adipocyte characteristics related to fat depot origin rather than adipocyte size per se limit cellular insulin responsiveness and glucose uptake in male C57BL/6J mice. These findings contribute to the overall understanding of factors limiting adipocyte function and how adipose progression affects insulin response and glucose transport capacity differently in diverse fat depots. Future studies examining whether the proposed characteristics hold true in adipocytes derived from female mice or human origin are needed. [ABSTRACT FROM AUTHOR]

When this project was designed, there was no evidence that adding resistant starch to available carbohydrate (avCHO) reduced glycaemic and insulinaemic responses (GIR). We compared GIR elicited by a cookie containing cross-linked phosphorylated RS4 wheat starch (Fibersym®) (RS4XL) versus an avCHO-matched control-cookie (CC) after n = 15 adults had consumed RS4XL or CC daily for 3-days using a double-blind, randomised, cross-over design. The difference in glucose iAUC over 0–2 h (primary endpoint) (mmol × min/L) after RS4XL, (mean ± SEM) 106 ± 16, versus CC, 124 ± 16, was not significant (p = 0.087). However, RS4XL reduced 0–90 min glucose iAUC (72 ± 9 vs 87 ± 9, p = 0.022), peak glucose concentration (6.05 ± 0.36 vs 6.57 ± 0.31 mmol/L, p = 0.017) and 0–2 h insulin iAUC (189 ± 21 vs 246 ± 24 nmol × h/L, p = 0.020). These results show that RS4XL reduced postprandial glycaemic and insulinaemic responses when added to avCHO, but do not prove that the products of its colonic fermentation are required for this effect. [ABSTRACT FROM AUTHOR]

Previous studies have reported inconsistent associations between low-carbohydrate diets (LCD) and plasma lipid profile. Also, there is little evidence on the role of the quality and food sources of macronutrients in LCD in cardiometabolic health. We investigated the cross-sectional associations between LCD and plasma cardiometabolic risk markers in a nationwide representative sample of the US population. Diet was measured through two 24-h recalls. Overall, healthy (emphasising unsaturated fat, plant protein and less low-quality carbohydrates) and unhealthy (emphasising saturated fat, animal protein and less high-quality carbohydrate) LCD scores were developed according to the percentage of energy as total and subtypes of carbohydrate, protein and fat. Linear regression was used to estimate the percentage difference of plasma marker concentrations by LCD scores. A total of 34 785 participants aged 18–85 years were included. After adjusting for covariates including BMI, healthy LCD was associated with lower levels of insulin, homoeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP) and TAG, and higher levels of HDL-cholesterol, with the percentage differences (comparing extreme quartile of LCD score) of −5·91, −6·16, −9·13, −9·71 and 7·60 (all P trend < 0·001), respectively. Conversely, unhealthy LCD was associated with higher levels of insulin, HOMA-IR, CRP and LDL-cholesterol (all P trend < 0·001). Our results suggest that healthy LCD may have positive, whereas unhealthy LCD may have negative impacts on CRP and metabolic and lipid profiles. These findings underscore the need to carefully consider the quality and subtypes of macronutrients in future LCD studies. [ABSTRACT FROM AUTHOR]

The properties of each food, composition, and structure affect the digestion and absorption of nutrients. Dietary fiber (DF), especially viscous DF, can contribute to a reduction in the glycemic response resulting from the consumption of carbohydrate-rich foods. Target and control of postprandial glycemic values are critical for diabetes prevention and management. Some mechanisms have been described for soluble DF action, from the increase in chyme viscosity to the production of short-chain fatty acids resulting from fermentation, which stimulates gastrointestinal motility and the release of GLP-1 and PYY hormones. The postprandial glycemic response due to inulin and resistant starch ingestion is well established. However, other soluble dietary fibers (SDF) can also contribute to glycemic control, such as gums, β-glucan, psyllium, arabinoxylan, soluble corn fiber, resistant maltodextrin, glucomannan, and edible fungi, which can be added alone or together in different products, such as bread, beverages, soups, biscuits, and others. However, there are technological challenges to be overcome, despite the benefits provided by the SDF, as it is necessary to consider the palatability and maintenance of their proprieties during production processes. Studies that evaluate the effect of full meals with enriched SDF on postprandial glycemic responses should be encouraged, as this would contribute to the recommendation of viable dietary options and sustainable health goals. [ABSTRACT FROM AUTHOR]

Poor growth performance and metabolic disorders are prevalent problems in lambs exposed to maternal heat stress, specifically during the last midthird of gestation. Columbia–Rambouillet crossbred lambs (n = 12) were immediately separated from their heat-stressed and non-stressed dam at lambing. The maternal heat stress exposure occurred during the last mid-third gestation and was for about 40 d (40 to 80 d). Lamb body weight (BW) was recorded daily for 4 mo. A glucose tolerance test was performed in mo 4 to evaluate glucose concentrations and insulin response. Maternal heat-stressed lamb (HS) presented reduced BW throughout the experimental time (P < 0.05) than maternal thermoneutral lamb (TN; CN = 12.69 ± 0.29 kg and HS = 9.89 ± 0.29 kg). Glucose concentrations were similar between environmental conditions (P > 0.05). Neither the insulin response presented a significance (P > 0.05) between those lambs exposed to HS and TN conditions during gestation. Although maternal exposure to HS can affect performance of the offspring throughout life, metabolic disorders associated with insulin resistance are not a problem at 4 mo. However, preliminary data showed that these same lambs at 8 mo old and 11 mo old show an irregular insulin response in maternal heat-stressed lambs that can persist throughout the life of the offspring. [ABSTRACT FROM AUTHOR]

This research investigated the effects of gluten free diet (GFD) on nutritional intake, glycaemic and insulin response. In a cross-sectional study, participants who consumed gluten-containing diet (GCD; n = 11) and GFD (n = 11) completed a food diary, blood glucose and insulin measurements. In a pre-post intervention study (n = 11), glycaemic and insulin responses were tested before and after four weeks of a GFD. Food intake was recorded before and after two weeks. No significant differences in nutrient intake, glycaemic or insulin responses were found in the cross-sectional study. In the intervention study, there was a significant reduction in body weight (p =.007) and body mass index (BMI) (p =.004) after four weeks and lower thiamine intake (p =.021) after two weeks of GFD. Glycaemic response was significantly higher (p <.05) following GFD with no differences in insulin response. These differences were not evident if GFD was followed for a longer period, possibly due to improved food choices. [ABSTRACT FROM AUTHOR]

Background: Structure and protein-starch interactions in pasta products can be responsible for lower postprandial glycemic responses compared with other cereal foods.Objectives: We tested the effect on postprandial glucose metabolism induced by 2 pasta products, couscous, and bread, through their structural changes during mastication and simulated gastric digestion.Methods: Two randomized controlled trials (n = 30/trial) in healthy, normal-weight adults (mean BMI of 23.9 kg/m2 (study 1) and 23.0 kg/m2 (study 2)) evaluated postprandial glucose metabolism modulation to portions of durum wheat semolina spaghetti, penne, couscous, and bread each containing 50 g available carbohydrate. A mastication trial involving 26 normal-weight adults was conducted to investigate mastication processes and changes in particle size distribution and microstructure (light microscopy) of boluses after mastication and in vitro gastric digestion.Results: Both pasta products resulted in lower areas under the 2-h curve for blood glucose (-40% for spaghetti and -22% for penne compared with couscous; -41% for spaghetti and -30% for penne compared with bread), compared with the other grain products (P < 0.05). Pasta products required more chews (spaghetti: 34 ± 18; penne: 38 ± 20; bread: 27 ± 13; couscous: 24 ± 17) and longer oral processing (spaghetti: 21 ± 13 s; penne: 23 ± 14 s; bread: 18 ± 9 s; couscous: 14 ± 10 s) compared with bread or couscous (P < 0.01). Pastas contained more large particles (46-67% of total particle area) compared with bread (0-30%) and couscous (1%) after mastication and in vitro gastric digestion. After in vitro gastric digestion, pasta samples still contained large areas of nonhydrolyzed starch embedded within the protein network; the protein in bread and couscous was almost entirely digested, and the starch was hydrolyzed.Conclusions: Preservation of the pasta structure during mastication and gastric digestion explains slower starch hydrolysis and, consequently, lower postprandial glycemia compared with bread or couscous prepared from the same durum wheat semolina flour in healthy adults.The postprandial in vivo trials were registered at clinicaltrials.gov as NCT03098017 and NCT03104686. [ABSTRACT FROM AUTHOR]

The depot differences between Subcutaneous Fat (SAF) and Visceral Fat (VAF) are critical for human well-being and disease processes in regard to energy metabolism and endocrine function. Miniature pigs (Sus scrofa) are ideal biomedical models for human energy metabolism and obesity due to the similarity of their lipid metabolism with that of humans. However, the regulation of differences in fat deposition and development remains unclear. In this study, the development of SAF and VAF was characterized and compared in Bama pig during postnatal development (infancy, puberty and adulthood), using RNA sequencing techniques (RNA-Seq). The transcriptome of SAF and VAF was profiled and isolated from 1-, 3- and 6 months-old pigs and identified 23,636 expressed genes, of which 1,165 genes were differentially expressed between the depots and/or developmental stages. Upregulated genes in SAF showed significant function and pathway enrichment in the central nervous system development, lipid metabolism, oxidation-reduction process and cell adhesion, whereas genes involved in the immune system, actin cytoskeleton organization, male gonad development and the hippo signaling pathway were preferentially expressed in VAF. Miner analysis of short time-series expression demonstrated that differentiation in gene expression patterns between the two depots corresponded to their distinct responses in sexual development, hormone signaling pathways, lipid metabolism and the hippo signaling pathway. Transcriptome analysis of SAF and VAF suggested that the depot differences in adipose tissue are not only related to lipid metabolism and endocrine function, but are closely associated with sexual development and organ size regulation. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetic population. Methods: A total of 446 people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) who participated in the Da Qing Diabetes Study, were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response. Results: Over 30 years, the rates of all cause death were 9.94, 14.81, 15.02, and 17.58 per 1000 person-years across the four groups respectively. The rate for cardiovascular disease (CVD) death was 5.14, 6.50, 6.80 and 10.47 per 1000 person-years. Compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR = 2.14, 95% CI 1.34–3.42), Q3 (HR = 1.94, 95% CI 1.20–3.14), and Q2 group (HR = 1.70, 95% CI 1.06–2.74). In the Fine-Gray model with non-CVD death as competing risk, the increased insulin AUC were also significantly associated with the CVD death (Q4 vs Q1, HR = 2.04, 95% CI 1.10–3.79). In the fractional polynomial regression analysis, a nonlinear association between insulin AUC and all-cause and CVD death was demonstrated. In addition, insulin AUC was associated with a progressively higher risk of all-cause death and CVD death (fractional power 3, P < 0.001). Conclusion: A higher post-load insulin response was significantly associated with a long-term increased risk of all-cause and CVD deaths in the Chinese non-diabetic population. It suggests that people featured by this phenotype is a potential important target for further intervention. [ABSTRACT FROM AUTHOR]

Background: The RISE Pediatric Medication Study compared strategies for preserving β‐cell function, including a 9‐month follow‐up after treatment withdrawal to test treatment effect durability. Objective: Evaluate OGTT measures of glucose and β‐cell response through 12 months of intervention and 9 months of medication washout. Participants: Youth (n = 91) aged 10 to 19 years with BMI ≥85th percentile and impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (T2D). Methods: A multicenter randomized clinical trial comparing insulin glargine for 3 months followed by metformin for 9 months (G→Met) or metformin alone (Met) for 12 months. We report within‐group changes from baseline to end of medication intervention (M12), baseline to 9 months post‐medication withdrawal (M21), and end of medication (M12) to M21. OGTT C‐peptide index [CPI] paired with 1/fasting insulin evaluated β‐cell response. Results: At M12, both treatments were associated with stable fasting glucose (G→Met baseline 6.0 ± 0.1 vs M12 5.9 ± 0.2 mmol/L, P =.62; Met baseline 6.1 ± 0.2 vs M12 6.0 ± 0.2 mmol/L, P =.73) and 2‐hour glucose (G→Met baseline 10.2 ± 0.4 vs M12 9.3 ± 0.5 mmol/L, P =.03; Met baseline 10.2 ± 0.4 vs M12 10.6 ± 0.6 mmol/L, P =.88). Following medication withdrawal, fasting glucose worsened (G→Met M21 8.6 ± 1.8, P =.004; Met M21 7.8 ± 0.7 mmol/L, P =.003), as did 2‐hour glucose (G→Met M21 13.2 ± 1.4, P =.002; Met M21 13.1 ± 1.2 mmol/L, P =.006), associated with declines in β‐cell response. Conclusions: G→Met and Met were associated with stable glucose measures during 12 months of treatment in youth with IGT or recently diagnosed T2D. Glucose and β‐cell response worsened post‐medication withdrawal, suggesting treatment must be long‐term or alternative treatments pursued. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34–37 weeks gestation, T1), to early postpartum (1–5 days, T2) and late postpartum (6–12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI. Methods: ISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75 g OGTT. Adipokines, cytokines and lipids were measured prior to each OGTT. Linear mixed-effects models were used to compare changes across each time point. Changes in ISOGTT, insulin response and DI were correlated with changes in maternal adipokines, cytokines and lipids at each time point. Results: A total of 27 women completed all assessments. Compared with T1, ISOGTT was 11.20 (95% CI 8.09, 14.31) units higher at 1–5 days postpartum (p < 0.001) and was 5.49 (95% CI 2.38, 8.60) units higher at 6–12 weeks postpartum (p < 0.001). Compared with T1, insulin response values were 699.6 (95% CI 957.5, 441.6) units lower at T2 (p < 0.001) and were 356.3 (95% CI 614.3, 98.3) units lower at T3 (p = 0.004). Compared with T1, the DI was 6434.1 (95% CI 2486.2, 10,381.0) units higher at T2 (p = 0.001) and was 4262.0 (95% CI 314.6, 8209.3) units higher at T3 (p = 0.03). There was a decrease in mean cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol from T1 to T2 (all p < 0.001), and an increase in mean C-reactive protein, IL-6 and IL-8 from T1 to T2 (all p < 0.001). Mean leptin decreased from T1 to T2 (p = 0.001). There was no significant change in mean adiponectin (p = 0.99) or TNF-α (p = 0.81) from T1 to T2. The mean maternal BMI decreased from T1 to T2 (p = 0.001) and T3 (p < 0.001). There were no significant correlations between any measure of change in ISOGTT, insulin response and DI and change in maternal cytokines, adipokines, lipids or weight from T1 to T2. Conclusions/interpretation: In women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6–12 weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight. Trial registration: ClinicalTrials.gov NCT02082301 [ABSTRACT FROM AUTHOR]

Refined carbohydrates result from milling techniques that remove the outer layers of a cereal grain and grind the endosperm into a flour ingredient that is devoid of dietary fiber. Technologies have been developed to produce high-amylose cereal grains that have a significantly higher resistant starch type 2 and thus dietary fiber content in the endosperm of the cereal grain, which has positive implications for human health. A review of the literature was conducted to study the effects of resistant starch type 2 derived from high-amylose grains on glucose and insulin response. While thousands of articles have been published on resistant starch, only 30 articles have focused on how resistant starch type 2 from high-amylose grains affects acute and long-term responses of glucose and insulin control. The findings showed that resistant starch has the ability to attenuate acute postprandial responses when replacing rapidly digestible carbohydrate sources, but there is insufficient evidence to conclude that resistant starch can improve insulin resistance and/or sensitivity. [ABSTRACT FROM AUTHOR]

Legumes, such as black beans (Phaseolus vulgaris L.) and chickpeas (Cicer arietinum L.), have a low glycemic index, and may reduce the glycemic load of meals in which they are included. Although the low glycemic response of beans consumed alone has been documented, few studies have examined the glycemic response to traditional food combinations such as black beans and rice or chickpeas and rice. This randomized cross-over study examined the glycemic and insulinemic impact of 50 grams of available carbohydrate from three test meals: plain white rice (control), black beans with rice, and chickpeas with rice among healthy adult women (n = 12, 18-65 years). Treatments were consumed on different mornings, a minimum of 7 days apart. Blood samples were collected at time 0 (fasting), and at 30, 60,90, and 120 min postprandial, and were subsequently analyzed for glucose and insulin concentrations. Glucose response based on the incremental area under the curve showed a significant difference by treatment (p = 0.027). Changes in blood glucose concentrations were significantly different for the black bean meal and the chickpea meal in comparison to rice alone at 60 min (p = 0.026 and p = 0.024), 90 min (p = 0.001 and p = 0.012) and 120 min post prandial (p = 0.024; black bean meal). Findings indicate that combinations of black beans and chickpeas with white rice improve glycemic response, providing evidence that has promising implications for dietary guidance to reduce postprandial glucose and related health risks through traditional food patterns. [ABSTRACT FROM AUTHOR]

Background/Aims: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Methods: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Results: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test ( p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 ( p < 0.0001) and GIP response ( p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly ( p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. Conclusions: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. [ABSTRACT FROM AUTHOR]

Purpose: Efforts regarding the amelioration of postprandial glycemic response to bread are mainly focused in the addition of soluble dietary fibers. The current study presents another approach which is based on the supplementation of flour with Cr-enriched yeast. Cr is known for its beneficial effects on improvement of glucose tolerance and enhancement of insulin sensitivity. Methods: Twelve normoglycemic subjects were provided with white bread (WB, reference food) or whole wheat bread with Cr-enriched yeast (WWCrB, rich in insoluble fibers) or white wheat bread with Cr-enriched yeast (WCrB, poor in fibers) or whole wheat-rye-barley bread enriched with oat beta glucans (BGB, rich in soluble fibers) with 1-week intervals in amounts that yielded 50 g of available carbohydrates. Postprandial glucose, insulin and ghrelin responses as well as glycemic index (GI) were evaluated. Results: Ingestion of WWCrB, WCrB and BGB elicited lower incremental area under the curve (iAUC) for 120-min glycemic response compared to WB (1033.02 ± 282.32, 701.69 ± 330.86 and 748.95 ± 185.42 vs 2070.87 ± 518.44 mg/dL min, respectively, P < 0.05 for WCrB and BGB). The GI was calculated as 62.35 ± 11.78 for WWCrB, 34.22 ± 11.93 for WCrB and 37.90 ± 5.00 for BGB ( P < 0.05 vs WB, GI = 100). iAUC for 120-min insulin response to BGB was significantly lower than WB (2780.04 ± 303.26 vs 3915.53 ± 490.57 μU/mL min, P < 0.05), while ghrelin remained suppressed for almost 120 min after the consumption of WWCrB and BGB. Conclusions: Supplementation of flour with Cr-enriched yeast induces milder postprandial glycemic response to bread without the necessity of high fiber amounts, providing with another strategy for the management of glycemic control. [ABSTRACT FROM AUTHOR]

Aim Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5-T2) exerts T3-like effects on energy consumption and lipid metabolism. 3,5-T2 also improves glucose tolerance in rats and 3,5-T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5-T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5-T2 and another form of T2 (3,3-T2) in a mouse model of diet-induced obesity and determined effects of T3 and 3,5-T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose. Methods Cell- and protein-based assays of thyroid hormone action. Assays of metabolic parameters in mice. Analysis of transcript and protein levels in different tissues by qRT- PCR and Western blot. Results T3 and 3,5-T2 both reduce body weight, adiposity and body temperature despite increased food intake. 3,3′-T2 lacks these effects. T3 and 3,5-T2 reduce blood glucose levels, whereas 3,3′-T2 worsens glucose tolerance. Neither T3 nor 3,5-T2 affects markers of insulin sensitization in skeletal muscle or white adipose tissue ( WAT), but both reduce hepatic GLUT2 glucose transporter levels and glucose output. T3 and 3,5-T2 also induce expression of mitochondrial uncoupling proteins ( UCPs) 3 and 1 in skeletal muscle and WAT respectively. Conclusions 3,5-T2 influences glucose metabolism in a manner that is distinct from insulin sensitization and involves reductions in hepatic glucose output and changes in energy utilization. [ABSTRACT FROM AUTHOR]

Lowering postprandial glucose and insulin responses may have significant beneficial implications for prevention and treatment of metabolic disorders. Bread is a staple food consumed worldwide in a daily basis, and the use of different baking technologies may modify the glucose and insulin response. The aim of this review was to critically record the human studies examining the application of different bread making processes on postprandial glucose and insulin response to bread. Literature is rich of results which show that the use of sourdough fermentation instead of leavening with Saccharomyces cerevisiae is able to modulate glucose response to bread, whereas evidence regarding its efficacy on lowering postprandial insulin response is less clear. The presence of organic acids is possibly involved, but the exact mechanism of action is still to be confirmed. The reviewed data also revealed that the alteration of other processing conditions (method of cooking, proofing period, partial baking freezing technology) can effectively decrease postprandial glucose response to bread, by influencing physical structure and retrogradation of starch. The development of healthier bread products that benefit postprandial metabolic responses is crucial and suggested baking conditions can be used by the bread industry for the promotion of public health. [ABSTRACT FROM PUBLISHER]

Starch digestibility may have an effect on the postprandial blood glucose profile. The aim of this meta-analysis was to analyze the relationship between Slowly Digestible Starch (SDS) levels and plasma glucose appearance and disappearance rates, as well as other parameters of glucose metabolism, after healthy subjects consumed cereal products that differed in SDS content. Three randomized controlled clinical trials that included a total of 79 subjects were identified. Using binary classification for the variables (high versus low levels, more than 12 g of SDS per portion, and less than 1 g of SDS per portion, respectively), we found that there was a 15-fold higher chance of having a low rate of appearance of exogenous glucose (RaE) after consumption of a high-SDS product. A high SDS content was also associated with a 12-fold and 4-fold higher chance of having a low rate of disappearance of exogenous glucose (RdE) and rate of disappearance of total plasma glucose (RdT), respectively. The RaE kinetics were further analyzed by modeling the contribution of SDS content to the different phases of the RaE response. We show that the higher the SDS content per portion of cereal product, the higher its contribution to the incremental area under the curve (iAUC) of the RaE response after 165 min. Using the association rule technique, we found that glycemic iAUC and insulinemic iAUC values vary in the same direction. In conclusion, this meta-analysis confirms the effect of the SDS level in cereal products on the metabolic response, and shows for the first time that the degree to which SDS affects the RaE response differs depending on the SDS content of the food product, as well as the phase of the postprandial period. [ABSTRACT FROM AUTHOR]

Insulin regulates a wide range of metabolic processes in mammals, such as homeostasis and the breakdown of glucose. Recently, the existence of an insulin-related growth factor in maize (ZmIGF) and a possible receptor for this growth factor has been reported. This peptide exerts effects on plant growth and promotes germination by activating the target of rapamycin (TOR) signaling pathways, which is similar to the insulin response in mammals. In this study, we analyzed the insulin response in maize embryos using a proteomic approach. Our results indicated that insulin modulates the expression of proteins involved in processes, such as storage protein degradation, protein processing, redox and desiccation stress, and glucose metabolism. The involvement of TOR signaling pathways was analyzed using the TOR inhibitor, rapamycin. The results showed that the modulation of these proteins by insulin is independent of the TOR pathway. These results indicated that insulin promotes changes in metabolism-related proteins to ensure successful germination in maize. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine if omega-3 (n-3) supplementation combined with acute aerobic exercise would improve glucose and insulin responses in normoglycemic, inactive, overweight men.Methods: In a random order, ten inactive and normoglycemic men (30.6 ± 10 years, 85.4 ± 11 kg, 26.7 ± 4 BMI) completed a rest (R) and exercise trial (EX) without n-3 supplementation. Following 42 days of n-3 supplementation, participants again completed a rest (R + n-3) and exercise trial (EX + n-3) with continued n-3 supplementation. The exercise trial consisted of 3 days of ~70 % VO2peak for 60 min/session. N-3 supplementation entailed 4.55 g/day of n-3 (EPA 2.45 g, DHA 1.61 g). A 75 g oral glucose tolerance (OGTT) test was administered 14-16 h after each trial.Results: Relative to R (35,278 ± 9169 pmol/L), EX without n-3 reduced the incremental area under the curve for insulin (iAUCinsulin) during an OGTT by 21.3 % (27765 ± 4925 pmol/L, p = 0.018) and 20.6 % after the EX + n-3 trial (27,999 ± 8370 pmol/L; p = 0.007). In addition, EX (96 ± 21 pmol/L; p = 0.006) reduced C-peptide by 13.5 % when compared to R (111 ± 26 pmol/L). No difference was observed between R and n-3 trials for iAUCinsulin and iAUCC-peptide. Only EX improved insulin sensitivity index by 5.6 % (p = 0.02) when compared to R.Conclusions: These data suggest that n-3 supplementation does not add any additional benefit beyond the exercise induced insulin responses in inactive men. Furthermore, n-3 supplementation alone does not appear to impair insulin action in normoglycemic, inactive, overweight men. [ABSTRACT FROM AUTHOR]

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP4) which, in turn, associates with another serum protein, transthyretin (TTR), to form a ternary retinol-RBP4-TTR complex. At some tissues, retinol-bound (holo-) RBP4 is recognised by a receptor termed stimulated by retinoic acid 6 (STRA6) which transports retinol into cells. This mini-review summarises evidence demonstrating that, in addition to functioning as a retinol transporter, STRA6 is also a signalling receptor which is activated by holo-RBP4. The data show that STRA6-mediated retinol transport induces receptor phosphorylation, in turn activating a Janus kinases2/signal transducers and activators of transcription (STAT)3/5 cascade that culminates in induction of STAT target genes. STRA6-mediated retinol transport and cell signalling are inter-dependent, and both functions critically rely on intracellular retinol trafficking and metabolism. Hence, STRA6 couples ‘sensing’ of vitamin A homeostasis and metabolism to cell signalling, allowing it to control important biological functions. For example, by inducing the expression of the STAT target gene suppressor of cytokine signalling 3, STRA6 potently suppresses insulin responses. These observations provide a rationale for understanding the reports that elevation in serum levels of RBP4, often observed in obese mice and human subjects, causes insulin resistance. The observations indicate that the holo-RBP4 /STRA6 signalling cascade may comprise an important link through which obesity leads to insulin resistance and suggest that the pathway may be a novel target for treatment of metabolic diseases. [ABSTRACT FROM PUBLISHER]

Consumption of high glycaemic index (GI) and glycaemic response (GR) food such as white rice has been implicated in the development of type 2 diabetes. Previous studies have reported the ability of individual amino acids to reduce GR of carbohydrate-rich foods. Because of the bitter flavour of amino acids, they have rarely been used to reduce GR. We now report the use of a palatable, preformed amino acid mixture in the form of essence of chicken. In all, sixteen healthy male Chinese were served 68 or 136 ml amino acid mixture together with rice, or 15 or 30 min before consumption of white rice. Postprandial blood glucose and plasma insulin concentrations were measured at fasting and every 15 min after consumption of the meal until 60 min after the consumption of the white rice. Subsequent blood samples were taken at 30-min intervals until 210 min. The co-ingestion of 68 ml of amino acid mixture with white rice produced the best results in reducing the peak blood glucose and GR of white rice without increasing the insulinaemic response. It is postulated that amino acid mixtures prime β-cell insulin secretion and peripheral tissue uptake of glucose. The use of ready-to-drink amino acid mixtures may be a useful strategy for lowering the high-GI rice diets consumed in Asia. [ABSTRACT FROM PUBLISHER]

Aims/hypothesis: Maternal metabolic alterations are essential to achieve healthy pregnancy outcomes, but increasing maternal parity may be associated with long-term metabolic dysfunction risk. As existing data are limited by study design, our aim was to employ robust metabolic measures to determine whether or not physiological pregnancy alterations in maternal metabolic function persist at 1 year postpartum. Methods: We evaluated 21 healthy women, of whom 11 had an interval pregnancy (IP) and assessment at preconception, during pregnancy and 1 year postpartum, and 10 had no IP and assessment at baseline and a 1 year interval. Assessment measures included body composition, insulin sensitivity and response, and basal metabolic rate. For each measure, IP vs no IP and time intervals within each group were compared using nonparametric analyses, reporting median (IQR). Results: IP and no IP women were similar at enrolment, and no IP women had similar metabolic profiles at enrolment and the 1 year interval. IP women exhibited expected metabolic changes during pregnancy compared with preconception. In IP women, preconception and postpartum measures, including fat mass (20.7 [13.7-37.4] kg vs 18.4 [13.8-41.3] kg; p = 0.2), total insulin response (AUC 11,459 [9,230-13,696] pmol/ml × min vs 11,522 [5,882-17,404] pmol/ml × min; p = 0.9), insulin sensitivity (0.12 [0.06-0.13] mg [kg fat-free mass (FFM)] min vs 0.11 [0.10-0.15] mg [kg FFM] min; p = 0.1) and basal metabolic rate (0.092 [0.092-0.105] kJ min FFM vs 0.096 [0.088-0.096] kJ min FFM; p = 0.5), were similar. Conclusions/interpretation: Our findings suggest pregnancy might not irreversibly alter maternal metabolic profile, measured at preconception through to 1 year postpartum. This result might be explained by a return to pre-pregnancy weight. [ABSTRACT FROM AUTHOR]

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance. [ABSTRACT FROM AUTHOR]

Asians exhibit larger glycaemic response (GR) and insulin response (IR) than Caucasians, predisposing to an increased risk of type 2 diabetes mellitus (T2DM). We aimed to determine the GR and IR as well as the glycaemic index (GI) and insulinaemic index (II) of two rice varieties among three ethnic groups in Singapore. A total of seventy-five healthy males (twenty-five Chinese, twenty-five Malay and twenty-five Asian-Indians) were served the available equivalent carbohydrate amounts (50 g) of test foods (Jasmine rice and Basmati rice) and a reference food (glucose) on separate occasions. Postprandial blood glucose and plasma insulin concentrations were measured at fasting ( − 5 and 0 min) and at 15, 30, 45, 60, 90 and 120 min after food consumption. Using the trapezoidal rule, GR, IR, GI and II values were determined. The GR did not differ between ethnic groups for Jasmine rice and Basmati rice. The IR was consistently higher for Jasmine rice (P= 0·002) and Basmati rice (P= 0·002) among Asian-Indians, probably due to compensatory hyperinsulinaemia to maintain normoglycaemia. The GI and II of both rice varieties did not differ significantly between ethnicities. The overall mean GI for Jasmine rice and Basmati rice were 91 (sd 21) and 59 (sd 15), respectively. The overall mean II for Jasmine rice was 76 (sd 26) and for Basmati rice was 57 (sd 24). We conclude that the GI values presented for Jasmine rice and Basmati rice were applicable to all three ethnic groups in Singapore. Future studies should include deriving the II for greater clinical utility in the prevention and management of T2DM. [ABSTRACT FROM PUBLISHER]

Aims Glucagon-like peptide-1 ( GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo. Methods Two single-centre, double-blind, randomized, placebo-controlled, single-dose, crossover studies were performed in healthy subjects ( HS) and people with type 2 diabetes mellitus ( T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first- and second-phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate ( Kglucose). LIXI exposure was measured over 12 h. Results LIXI 20 µg reached maximum concentration after 2 h and resensitized first-phase insulin secretion by 2.8-fold in T2DM to rates comparable with those in HS on placebo, and raised second-phase insulin secretion by 1.6-fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8-fold in T2DM. First-phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second-phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short-lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS. Conclusions LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter-regulation to low glucose levels by glucagon. [ABSTRACT FROM AUTHOR]

Adiponectin (Ad) is a potent insulin-sensitizing adipokine that has been found to activate pathways involved in the adaptation to exercise. Therefore, we examined whether Ad is required for the increased insulin response observed following exercise training in Ad knockout mice (Ad KO). Eight weeks of exercise training significantly increased glucose and insulin tolerance in both wild type ( WT) and Ad KO mice. There were no differences in glucose tolerance between genotypes but insulin tolerance was improved to a greater extent in Ad KO compared to WT mice following exercise training (+26%, P < 0.05). There were no genotype differences in the insulin-stimulated phosphorylation of AKT or AS160 in red or white gastrocnemius muscle ( RG, WG). Exercise training increased total AKT and AS160 protein content in RG and total AS160 protein content in WG. There were no genotype differences in total AKT or AS160. However, exercise training induced a more robust increase in total AS160 in RG from Ad KO (+44 ± 8%, P < 0.05) compared to WT mice (+28 ± 7%, P = 0.06). There were no differences in total GLUT4 or FAT/ CD36 in RG or WG in WT or Ad KO, with or without exercise training. Similarly, there were no differences in RER, VO2, or activity between any groups. Our results indicate the presence of Ad is not required for exercise-induced increases in insulin response. Furthermore, it appears that exercise may improve insulin sensitivity to a greater extent in the absence of Ad, suggesting the presence of an unknown compensatory mechanism. [ABSTRACT FROM AUTHOR]

Background: A number of different pathways to obesity with different metabolic outcomes are recognised. Prenatal undernutrition in rats leads to increased fat deposition in adulthood. However, the form of obesity is metabolically distinct from obesity induced through other pathways (e.g. diet-induced obesity). Previous rat studies have shown that maternal undernutrition during pregnancy led to insulin hyper-secretion and obesity in offspring, but not to systemic insulin resistance. Increased muscle and liver glycogen stores indicated that glucose is taken up efficiently, reflecting an active physiological function of these energy storage tissues. It is increasingly recognised that adipose tissue plays a central role in the regulation of metabolism and pathophysiology of obesity development. The present study investigated the cell size and endocrine responsiveness of subcutaneous and visceral adipose tissue from prenatally undernourished rats. We aimed to identify whether these adipose tissue depots contribute to the altered energy metabolism observed in these offspring. Methods: Adipocyte size was measured in both subcutaneous (ScAT) and retroperitoneal adipose tissue (RpAT) in male prenatally ad libitum fed (AD) or prenatally undernourished (UN) rat offspring. Metabolic responses were investigated in adipose tissue explants stimulated by insulin and beta3 receptor agonists ex vivo. Expression of markers of insulin signalling was determined by Western blot analyses. Data were analysed by unpaired t-test or Two Way ANOVA followed by Fisher′s PLSD post-hoc test, where appropriate. Results: Adipocytes in offspring of undernourished mothers were larger, even at a lower body weight, in both RpAT and ScAT. The insulin response of adipose tissue was reduced in ScAT, and statistically absent in RpAT of UN rats compared with control. This lack of RpAT insulin response was associated with reduced expression of insulin signalling pathway proteins. Adrenergic receptor-driven lipolysis was observed in both adipose depots; however insulin failed to express its anti-lipolytic effect in RpAT in both, AD and UN offspring. Conclusions: Metabolic dysregulation in offspring of undernourished mothers is mediated by increased adipocyte size and reduced insulin responsiveness in both ScAT and especially in RpAT. These functional and morphological changes in adipocytes were accompanied by impaired activity of the insulin signalling cascade highlighting the important role of different adipose tissue depots in the pathogenesis of metabolic disorders. [ABSTRACT FROM AUTHOR]

Consequences of prenatal exposure to ethanol (E) include morphological, physiological, and cognitive deficits and are collectively classified as fetal alcohol spectrum disorders. Adult prenatal E exposed offspring show insulin resistance, and given that in utero hyperglycemic environment can cause metabolic disorders in subsequent generations; we investigated the effects of grandmaternal E on functional glucose and insulin responses of the second generation. Sprague-Dawley (S) rat dams, mated with S males, received E-containing liquid diet and two different control diets between gestational days 8 and 20. Additionally, because prenatal E-induced behavioral deficits can be reversed by simultaneous thyroxine (T4) treatment, another group of dams received 0.3 mg/l T4 in their E diet. Their first-generation (F1) offspring were mated with control Brown Norway (B) males or females to produce SB and BS F2 progeny. Dams consuming E during pregnancy were hyperglycemic, and their F1 offspring showed insulin resistance in the glucose tolerance test (GTT). However, F2 responses to GTT varied based on the sex of prenatal E-exposed parent. BS F2 females, and both male and female SB F2 progeny, displayed hypoglycemic and hyperinsulinemic GTT response patterns. Although administering T4 to E dams normalized thyroid function of the F1 generation, it did not reverse their prenatal E-induced metabolic dysfunction. In contrast, administration of T4 to the alcohol-consuming grandmother reversed or alleviated the aberrant GTT responses of the F2 progeny. Prenatal E-induced dysregulation of glucose metabolism can affect the next generation, possibly via ethanol effects on the germline of the F1 fetus. [ABSTRACT FROM AUTHOR]

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Background: Strong epidemiological evidence suggests that coffee consumption is associated with lower risk of type 2 diabetes. In postprandial studies, however, caffeine consumption has been associated with impaired glucose regulation. Aim of the study: To study the acute effects of coffee and caffeine-containing soft drinks on glycaemic and insulinaemic responses. Design: Twelve healthy volunteers were served each test food once and the reference glucose solution twice, containing 50 g of available carbohydrates, after an overnight fast at 1-week intervals in a random order. Capillary blood samples were drawn at 15-30 min intervals for 2 h after each study meal. The incremental areas under the curve (IAUC), glycaemic index (GI) and insulinaemic index (II), were calculated to estimate the glycaemic and insulinaemic responses. Results: Glucose and insulin responses of coffees with glucose containing 150 or 300 mg of caffeine did not differ from responses of pure glucose solution; the GIs were 104 and 103, and the IIs were 89 and 92, respectively. When a bun or sucrose and milk were consumed together with coffee, lower GI values and insulin responses were observed, reflecting the carbohydrate quality and protein content of the accompaniments. Sucrose-sweetened cola produced a high GI value of 90 and an II of 61. Conclusions: Coffee does not modify glycaemic and insulinaemic responses when ingested with a carbohydrate source. Therefore, there is no need to avoid coffee as a choice of beverage in GI testing. [ABSTRACT FROM AUTHOR]

Purpose – Starchy foods have been emphasized in the diet for reducing hyperglycemia and hyperinsulinemia. However, all starch containing foods respond differently, depending upon various other factors in food such as the amylose:amylopectin ratio, co-ingredients, methods of cooking, etc. which also impact its metabolic response. During days of fast, in India, potato and sago are the most commonly used food to provide quick source of energy. The purpose of this paper is to determine the functional and nutritional quality of fasting foods such as potato and sago, having higher amylopectin content, with respect to their relative glycemic and insulin response in normal healthy volunteers. Design/methodology/approach – The postprandial glycemic response to boiled potato and sago khichdi in relation to equal quantity of bread (reference) was compared using Relative Glycemic Potency (RGP) represented as the Glycemic Bread Equivalent (GBE) of foods. Five clinically healthy subjects were fed 100 g of test foods and standard, and their blood glucose and insulin response was recorded at fasting (0 min) and at 30, 60, 90 and 120 min. Findings – It was found that both potato and sago khichdi produced peak glucose response at 30 min and levels returned to baseline within 60 min. The higher amylopectin content which facilitates faster absorption from the gastro-intestinal tract and into the cell results in the total area under the curve (AUC) glycemic response to potato and sago khichdi to be significantly lower than that of bread (p < 0.05). The total AUC insulin response to potato (p <0.05) and sago khichdi was also lower than that of bread. Practical implications – Therefore, starch-based foods rich in amylopectin lead to quicker absorption of sugar to supply the energy to the energy-deprived cells common in fasting condition. Originality/value – The paper shows that the starch present in these fasting foods is typically characterized by a higher amylopectin:amylose ratio. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We sought to characterise novel genes dysregulated by sex hormonal imbalances that induce obesity and metabolic disorder in a setting of oestrogen deficiency and androgen dominance in follicle-stimulating hormone receptor ( For [also known as Fshr]) knockout female mice. Methods: Transcriptome analysis of mesenteric adipose tissue (MAT) of mutants revealed novel genes. One novel gene named Meda-7 was selected for study. Meda-7 was cloned from mouse and human adipose tissue; its expression, hormonal regulation and function were characterised. Results: Mouse Meda-7 is richly expressed in deep visceral adipose tissue and encodes a 22 kDa secreted protein with 71% homology to human mesenteric oestrogen-dependent adipose gene- 7 (MEDA-7) protein. Both have six conserved cysteines like many cytokines. In obese patients, MEDA-7 is more abundant in omental than subcutaneous fat. Meda-7 is downregulated in For-knockout female MAT at 5 months (obese state) followed by steep upregulation at 9 months (prediabetic condition) when mutants progress towards the metabolic syndrome. Meda-7 is expressed predominantly in the stromal-vascular cell fraction. In this fraction,M1-proinflammatorymacrophages are rich in Meda-7. Meda-7 dysregulation in 5-month-old For-knockout MAT is restored by oestrogen, but treatment has no effect in older mutants. Overabundance of MEDA-7 in HEK-293 cells enhances cell proliferation via p42/44 mitogen-activated protein kinases. Secreted MEDA-7 attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes, while downregulating glucose transporter-4 and upregulating both monocyte chemotactic protein-1 and suppressor of cytokine signalling-3. Downstream activity of the insulin signalling mediator, phospho-AKT, is also downregulated. Conclusions/interpretation: MEDA-7 is a hormone-regulated adipokine/proinflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. [ABSTRACT FROM AUTHOR]

Potatoes, especially mashed potatoes, are known to result in high glycaemic and insulinaemic responses. However, in most meals, potatoes are accompanied by other foods. The objective of the present study was to investigate how glycaemic and insulinaemic responses to a mashed potato meal changed when a high-fat food (rapeseed oil), a high-protein food (chicken breast) and/or salad were added to the meal. Healthy subjects (n 11) ingested the test meals once and the reference food (glucose solution) twice in a random order at 1-week intervals. Capillary blood samples were then drawn for 2 h, and glucose and insulin were analysed. The 2 h glycaemic responses to six mashed potato-containing meals varied more than twofold. The glycaemic index (GI) of pure mashed potato was 108, whereas combined with chicken breast, rapeseed oil and salad, it was only 54. The latter GI also differed considerably from its predicted value of 103, which was based on the individual GI of the components of the meal. The insulinaemic indices of the mashed potato-based meals varied between 94 and 148. Chicken breast in the meal increased the insulinaemic response, and rapeseed oil diminished it. However, the insulinaemic response to mashed potato with chicken breast and rapeseed oil was lower than that to mashed potato alone. In conclusion, the protein, fat and salad contents of a meal exert considerable influence on the glycaemic and insulinaemic responses to mashed potatoes. Furthermore, the estimation of the GI of a mixed meal by calculation is imprecise. [ABSTRACT FROM PUBLISHER]

ims/hypothesis: A genome-wide association study in the Japanese population reported two genome-wide significant loci associated with type 2 diabetes of which the VPS13C/ C2CD4A/ C2CD4B locus was replicated in Europeans. We looked for potential associations between the diabetogenic VPS13C/ C2CD4A/ C2CD4B rs7172432 variant and diabetes-related intermediary traits. Methods: We genotyped the rs7172432 variant in the population-based Inter99 cohort ( n = 6,784) and analysed quantitative diabetes-related traits in 5,722 non-diabetic participants who all were examined by an OGTT. Results: The diabetes-associated A allele was associated with 0.60 cm higher waist circumference ( p = 0.004), 0.037 mmol/l higher fasting plasma glucose ( p = 4 × 10) and 0.11 mmol/l higher plasma glucose at 30 min during an OGTT ( p = 4 × 10). In analyses adjusted for concomitant insulin sensitivity levels the diabetogenic allele was associated with a lower acute glucose-stimulated insulin response (GSIR) as estimated by 30 min serum insulin ( β = −0.039, p = 2 × 10), insulinogenic index ( β = −0.057, p = 1 × 10) and BIGTT-acute insulin release ( β = −0.041, p = 9 × 10). As rs7172432 is situated in a region previously associated with glycaemic traits, we tested linkage disequilibrium (LD) with the reported regional lead single-nucleotide polymorphisms for fasting (rs11071657) and 2 h plasma glucose (rs17271305), and performed conditional analyses of rs7172432. Rs7172432 showed moderate LD with rs11071657 and rs17271305 ( R < 0.34) and we found strong association by almost unchanged effect sizes of rs7172432 with plasma glucose and estimates of GSIR in analyses conditional on rs11071657 and rs17271305. Conclusions/interpretation: The diabetogenic VPS13C/ C2CD4A/ C2CD4B rs7172432 A allele associates with GSIR in non-diabetic individuals from the general population, suggesting an impaired beta cell function as an intermediary diabetes-related trait. [ABSTRACT FROM AUTHOR]

It is speculated that the physical form (liquid or solid) of the food substrate has an independent effect on the body's satiety mechanisms. Using a balanced and controlled design, the objective of the present study was to determine the glycemic response (GR), insulin response (IR) and subjective feelings of satiety to two solid (rice [BR] and spaghetti) and two liquid (orange juice and a sugar-sweetened fruit drink [SSD]) foods. Ten healthy participants consumed volume (576 ml) and carbohydrate (50 g) matched portions of the above test foods following a 12-h fast. Blood samples were obtained for the ensuing 120 min for glucose and insulin determination. The subjects also completed visual analog scales (VAS) providing data on subjective feelings of hunger, fullness and satiety. Although there were some significant differences in the total incremental areas under the curve for the GR and IR to liquids and solids, there were notable distinctions in the pattern of the response curves. The BR and SSD elicited significantly different levels of subjective hunger, fullness and satiety. The VAS ratings for all four treatments were at or below baseline by 30 min post-consumption. There were no associations between the GR/IR and VAS ratings. Although the GR and IR were not different between liquids and solids, their differential response patterns could have an impact on satiety and merits further investigation. [ABSTRACT FROM AUTHOR]

The effects of wheat and rye breads made from whole-wheat grain (WWG), wheat aleurone flour (WAF) or rye aleurone flour (RAF) on net portal absorption of carbohydrate-derived nutrients (glucose, SCFA and lactate) and apparent insulin secretion were studied in a model experiment with catheterised pigs. The breads were similar in dietary fibre (DF, 120–125 g/kg DM) but differed in arabinoxylans (50–62 g/kg), β-glucans (4–9 g/kg) and content of soluble DF (13–29 g/kg). Six pigs in a repeated 3 × 3 crossover design were fitted with catheters in the portal vein and the mesenteric artery and a portal flow probe. Pigs were fed three meals daily (at 09.00, 14.00 and 19.00 hours), and blood profiles were collected repeatedly from 08.30 until 19.00 hours once weekly. Net portal absorption of glucose was similar among breads and between meals. In contrast, insulin secretion was lowest (P < 0·05) in pigs fed RAF bread (3·9 nmol/h), intermediate in pigs fed WAF bread (5·4 nmol/h) and highest in pigs fed WWG bread (5·9 nmol/h), indicating that RAF bread improved insulin economy. Portal concentrations of propionate, butyrate and valerate were high, intermediate and low (P < 0·05) when pigs were fed RAF, WAF and WWG breads, respectively. Insulin secretion was higher (P < 0·001), and portal absorption of SCFA was lower (P < 0·05) after the first daily meal than after the second daily meal (8·8 v. 4·4 nmol/h). A low insulin response was associated with high portal absorption of SCFA. In conclusion, RAF bread was able to improve insulin economy compared to WWG bread. [ABSTRACT FROM PUBLISHER]

The article presents a study which compares the effects of two beverages with different glycemic index (GI) towards the blood glucose and insulin responses among cyclists during exercise. It found out that both the high and low GI beverages decreased the glycemic response. The results indicate that the beverage with high GI greatly reduces the blood glucose level compared to the low GI beverage.

Streptozotocin-induced diabetes mellitus (STZ-DM) in rats is a model of type 1 diabetes, which is commonly used to study diabetes, but differs from human diabetic pathophysiology in its insulin resistance. An STZ-DM rat can be administered five times the dose of insulin compared to that of a diabetic patient. Thus, attaining normoglycaemia in STZ-DM rats with insulin injections is complicated, and it involves an obvious risk of overdosing before getting a response. This study was designed to investigate whether suboptimal treatment with long-acting insulin restores insulin sensitivity in the STZ-DM rat, and thus an approach to more closely mimic the human condition. Male Sprague-Dawley rats were made diabetic by means of a single intravenous injection of STZ (55 mg/kg body weight (BW)), resulting in an increase in blood glucose (BG) from 6.5 ± 0.2 to 22.5 ± 1.0 mmol/l (P ⩽ 0.05) within 24 h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 ± 1.1 mmol/l, and the response to a single injection of fast-acting insulin (Humalog, 5 IE/kg BW) was a 23% reduction in BG. Thereafter, the rats were treated daily with a suboptimal dose of long-acting insulin for a total of 7 days (Insulatard, 5 IE/kg per day), which resulted in a BG level of 19.4 ± 2.7. The response to fast-acting insulin after the suboptimal treatment was a 61% reduction in BG. Thereafter, the animals were vehicle-treated for another 7 days, which resulted in a response to fast-acting insulin similar to the initial values (-34%). Furthermore, the group treated with suboptimal doses of long-acting insulin had a longer duration of the reduction in BG (150 min, as opposed to 90 min in the vehicle-treated groups). We conclude that the development of a decreased insulin response occurs rapidly within the first 2 weeks after the onset of diabetes in STZ-DM rats. This leads to a brief and significantly reduced decrease in BG when fast-acting insulin is administered. The insulin response is increased by treatment with suboptimal doses of long-acting insulin, but rapidly decreases again when treatment is withdrawn. Regular administration of suboptimal insulin doses may provide an approach to eliminate the effects of a lowered insulin response. [ABSTRACT FROM AUTHOR]

Bread, a frequently consumed food, is an ideal vehicle for addition of ingredients that increase nutrient density and add health benefits. This experimental cross-over study sought to test the effect of a vegetable-enriched bread (VB) in comparison to commercial white bread (WB) and wheatmeal bread (WMB) on serum glucose, insulin response and subjective appetite suppression. On three separate occasions, 10 participants (23 ± 7 years) visited the laboratory and consumed after an overnight fast, in random order, a 75 g serve of WB, WMB or VB. Venous blood samples drawn twice before (0 min) and at 15, 30, 45, 60, 90 and 120 min after consumption of the bread were analysed for glucose and insulin. Participants rated their subjective feelings of hunger, fullness, satisfaction and desire to eat on a 150 mm Likert scale. The mean glucose iAUC over 120 min was not different among the breads. The mean insulin iAUC for the VB was significantly lower than the WB and WMB; difference VB and WB 12,415 pmol/L*minutes (95% CI 1918, 22,912 pmol/L*minutes, p = 0.025) and difference VB and WMB 13,800 pmol/L*minutes (95% CI 1623, 25,976 pmol/L*minutes p = 0.031). The VB was associated with a higher fullness feeling in the participants over the 120-min period. The consumption of VB was associated with less insulin release and higher satiety over 120 min which may be related to the higher fibre content and texture of VB. The role of vegetable and fruit fibres such as pectin in bread and insulin response should also be further explored. [ABSTRACT FROM AUTHOR]

The functional status indicator for vitamin D, for both safety and efficacy, is serum 25-hydroxyvitamin D concentration. Efficacy for several health endpoints requires levels of 80 nmol/L or higher. Toxicity occurs at levels of 500 nmol/L or higher. The input needed for efficacy, in addition to typical food and cutaneous inputs, will usually be 1000–2000 IU/day of supplemental cholecalciferol. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day). [ABSTRACT FROM AUTHOR]

Siraitia grosvenori Swingle (SG) is a traditional Chinese fruit used as a folk medicine. Its extract (SG-ex) contains potent sweet elements with a sweetness several hundred times higher than table sugar. We investigated the antidiabetic effect of SG-ex in the type 2 diabetic Goto–Kakizaki (GK) rat. Diabetic 7-week-old GK rats were fed a diet supplemented with 0·4 % of the SG-ex for 13 weeks, and its antidiabetic effects were evaluated. SG-ex had no effect on food intake or body weight. In oral glucose tolerance tests (OGTT), SG-ex supplementation improved the insulin response at 15 min (control, 63 (sem 6) pm; SG-ex, 107 (sem 20) pm; P < 0·05) and reduced the plasma glucose level at 120 min after the glucose administration (control, 18·5 (sem 0·8) mm; SG-ex, 14·8 (sem 0·7) mm; P < 0·05). The total amount of insulin in whole pancreas taken from fasting rats was higher in the SG-ex-supplemented group, which may explain the greater capacity to secrete insulin during the OGTT. Thiobarbituric acid-reactive substances in both the liver and the plasma were lower in the SG-ex-supplemented group, suggesting that an absorbable component in SG-ex has an antioxidative effect on lipid peroxidation, thereby counteracting the oxidative stress caused by a diabetic state. Excreted urine volume and urinary albumin level for 24 h were both reduced in the SG-ex-supplemented group, suggesting the attenuation of kidney damage that is caused by diabetes. These data indicate that SG-ex supplementation may prevent complications and attenuate pathological conditions for type 2 diabetes, along with its sweet characteristics. [ABSTRACT FROM PUBLISHER]

Aims/hypothesis: The prevalence of altered glucose metabolism in obese children and adolescents is growing at a significant rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds differ in their adaptive mechanisms to obesity-related insulin resistance. The aim of this study was to evaluate the early insulin response and insulin clearance in response to an oral glucose load in obese children and adolescents. Methods: Seven hundred and nine obese children and adolescents underwent an OGTT. Indices of the early insulin response and insulin clearance were compared in participants of White European, African American and Hispanic origin. Results: Participants of the three ethnic groups demonstrated similar mechanisms of adaptation to increasing insulin resistance, but with different magnitudes. African American subjects had a greater early insulin response and decreased insulin clearance than their White European and Hispanic counterparts. This happened regardless of whether the cohort was divided by glucose tolerance level or by level of insulin sensitivity. IGT across ethnic groups was characterised by a marked decline in the acute insulin response in the context of severe insulin resistance and very low insulin clearance. Conclusions/interpretation: In obese children and adolescents, mechanisms of adaptation to obesity related to insulin resistance are similar across ethnic groups. The greater early insulin response needed to maintain glucose tolerance in young people of ethnic minorities may partially explain their greater tendency to develop type 2 diabetes. [ABSTRACT FROM AUTHOR]

The development of rebound hypoglycaemia has been reported after pre-exercise carbohydrate (CHO) ingestion in some studies but not in others. Differences in the experimental design and factors such as the exercise intensity are likely to be responsible for the discrepancies between these studies. Exercise intensity might be a crucial factor since it affects both insulinaemia and glucose uptake. Therefore the aim of the present study was to compare the glycaemic and insulinaemic responses to exercise at different intensities after ingestion of a standardized pre-exercise CHO load. Eight moderately trained subjects consumed 75 g of glucose 45 min prior to 20 min of exercise at 40%, 65% or 80% maximal power output. Blood samples were collected before glucose ingestion, at 15 min intervals at rest and 5 min intervals during exercise. During exercise, measurements of heart rate and breath-by-breath analysis of expired gas were performed continuously. The trials were performed at [mean (SEM)] 55 (1), 77 (1) and 90 (1) percentages maximal oxygen uptake . At the onset of exercise, plasma glucose concentration returned to pre-ingestion levels, while the insulin concentration was more than three times higher than at rest [on average 57 (7) compared to 16 (1) μU·ml–1). During exercise, plasma glucose concentrations decreased during the first 5 min of exercise and then stabilized in all trials at concentrations that would not be considered to be hypoglycaemic. There were no significant differences in glucose or insulin concentrations between the three trials during exercise. These data suggest that the glycaemic response to ingestion of 75 g of CHO 45 min pre-exercise is similar during exercise of different intensities. [ABSTRACT FROM AUTHOR]

The glycaemic and insulinaemic responses to different carbohydrates vary and these have been suggested to affect performance. The purpose of the present study was to determine the effects of pre-exercise ingestion of glucose (GLU), galactose (GAL) and trehalose (TRE) on metabolic responses at rest and during exercise and on subsequent time-trial (TT) performance. Eight well-trained male cyclists completed three exercise trials separated by at least 3 days. At 45 min before the start of exercise subjects consumed 500 ml of a beverage containing 75 g of either glucose, galactose or trehalose. The exercise trials consisted of 20 min of submaximal steady-state exercise (SS) at 65% of maximal power output immediately followed by a [mean (SEM)] 702 (25) kJ TT. Plasma glucose concentration 15 min postprandial was significantly higher in GLU compared to GAL and TRE (P<0.05). This was accompanied by a more than twofold greater rise in plasma insulin concentration in GLU compared to GAL and TRE (118% and 145%, respectively). During SS exercise four subjects in GLU and one subject in TRE developed a rebound hypoglycaemia (plasma glucose concentration less than 3.5 mmol·l–1). No differences were observed in TT performance between the three trials. Pre-exercise ingestion of trehalose and galactose resulted in lower plasma glucose and insulin responses prior to exercise and reduced the prevalence of rebound hypoglycaemia. Despite the attenuated insulin and glucose responses at rest and during exercise following pre-exercise ingestion of galactose and trehalose, there was no difference in TT performance compared with pre-exercise ingestion of glucose. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease. Objective: We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults. Design: This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/ d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese [body mass index (in kg/m2): 27-36] hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered. Results: Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 ± 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol · min/L; 95% CI: -18 720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the wholegrain diet (0.07 × 10-4 mmol·kg-1·min-1 per pmol/L; 95% CI: 0.003 × 10-4, 0.144 × 10-4). Conclusion: Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease. [ABSTRACT FROM AUTHOR]

Aim: Data are inconsistent whether hyperinsulinemia might be associated with adrenal hyperandrogenism in young adults born with low birth weight (LBW). Method: We investigated the insulin and adrenal steroid production of 70 young LBW adults [33 women (birth weight: 1,795 ± 435 g) and 37 men (birth weight: 1,832 ± 337 g)]. Their results were compared to those of 30 controls (14 men, 16 women), born with normal weight. Results: In LBW women, we measured higher basal DHEA (33.5 ± 13.1 vs. 23.6 ± 8.7 nmol/l, p < 0.05), DHEAS (8.0 ± 2.3 vs. 6.3 ± 2.1 μmol/l, p < 0.05), androstenedione (8.3 ± 2.8 vs. 6.0 ± 2.2 nmol/l, p < 0.05) and cortisol (0.25 ± 0.07 vs. 0.20 ± 0.07 μmol/l, p < 0.05) levels and higher insulin response during oral glucose tolerance test (log.AUCins: 2.62 ± 0.06 vs. 2.57 ± 0.03, p < 0.05). DHEA levels correlated with fasting insulin levels (r = 0.45, p < 0.01) and insulin response (r = 0.33, p < 0.05). In LBW men, higher cortisol (0.27 ± 0.06 vs. 0.22 ± 0.06 μmol/l, p < 0.01) and SHBG (18.4 ± 10.4 vs. 12.7 ± 5.9 nmol/l, p < 0.05) levels were found. Conclusions: Our results suggest that modest hypercortisolism is present in young LBW adults. While the endocrine sequel of hypercortisolism raised insulin response and hyperandrogenism is detectable in apparently healthy young LBW women, it is absent in young LBW men. This suggests that gender-dependent mechanisms might play a role in the development of insulin resistance in LBW adults.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) represent important tools in medicine and nutrition as new biomarkers, and can act as mediators of nutritional and pharmacological interventions. The aim of the present study was to analyse the effect of grape pomace supplementation on the expression of seven selected miRNAs and their potential relationship with the observed positive effect on glycaemic control, in order to shed light on the mechanism underlying the beneficial effect of this dietary intervention. For this purpose, plasma samples were obtained from 49 subjects with metabolic syndrome. After supplementation with grape pomace (6 weeks), these subjects were categorised as responders (n = 23) or non-responders (n = 26) according to the changes in their fasting insulin rate. MiRNA expression at baseline and at the end of the supplementation was analysed by RT-PCR, and the MiRecords Database was used to identify potential target genes for the studied miRNAs. The increase observed in miR-23a in the whole cohort was present in both subgroups of participants. The increase in miR-181a was significant among non-responders but not responders. The decrease in miR-30c and miR-222 was found in the responders, but not in the non-responders. No changes were observed in miR-10a, miR-151a, miR-181a, and miR-let-7a expressions. After analysing these results, a potential involvement of the reduced expression of miR-30c and miR-222, two microRNAs associated with insulin resistance and diabetes, in the improvement of glycaemic control produced by grape pomace administration, can be proposed. Further research is needed to confirm the involvement of glycolytic enzymes, PI3K, AMPK, and IRS-1 in the effect of grape pomace, as suggested by the changes induced in microRNAs. [ABSTRACT FROM AUTHOR]

Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1c), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (> 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently ‘normal’ insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA1c levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA1c and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain. [ABSTRACT FROM AUTHOR]

Combined data on four rices differing in amylose content suggested that difference in the response or the increase in blood plasma insulin and glucose in man to ingested rice was a result of difference in Amylograph cooked paste consistency and amylose content rather than to difference in starch lipids and starch gelatinization temperature. [ABSTRACT FROM AUTHOR]