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Background. Chronic hepatitis B cirrhosis is often accompanied by glucose metabolism disorder, and intestinal microbiota was closely related to both cirrhosis and diabetes. There are few studies on the role of intestinal microbiota in hepatitis B liver cirrhosis and diabetes mellitus (LCDM). The purpose of this study was to investigate the characteristics of intestinal microbiota in patients with LCDM and to evaluate the relationship between the severity of intestinal microbiota imbalance and clinical significance. Methods. A case-controlled study was conducted. People who met the inclusion and exclusion criteria of chronic HBV-related liver cirrhosis (LC), LCDM, and healthy controls (HC) were enrolled in, and their fecal and blood samples were collected. The V3-V4 region of 16s rDNA gene of fecal microbiota was sequenced; the bioinformatics analysis including α-diversity, β-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) was performed; and the correlation between bacteria and clinical indexes was analyzed. Results. A total of 70 participants completed fecal and blood tests, including 20 HC, 20 LCDM, and 30 LC. The α diversity of intestinal microbiota in the LCDM decreased than that in the HC. The abundance of Proteobacteria, Streptococcus, Escherichia-Shigella, and Lactobacillus increased, while the abundance of Bacteroidota, Bacteroides, Prevotella, Faecalibacterium, and Lachnospira decreased in the LCDM compared with the HC. The abundance of Lactobacillus, Roseburia, and Veillonella and the degree of hepatitis B cirrhosis dysbiosis indicator (HBCDI) increased in the LCDM than in the LC. The abundance of Escherichia-Shigella, Veillonella, and Lactobacillus positively correlated with liver injury and fasting blood glucose (FBG) level. The abundance of Escherichia-Shigella, Veillonella, Streptococcus, and Lactobacillus increased more significantly when FBG and glycosylated hemoglobin level increased. Conclusion. Intestinal microbiota of patients with LCDM was significantly disordered, and the degree was more serious than that cirrhosis patients without diabetes. [ABSTRACT FROM AUTHOR]

Modern lifestyle-associated factors, such as high-calorie intake, high-fat diet (HFD), and excessive artificial light, are risk factors for glucose and lipid metabolism disturbances. Melatonin may be beneficial for managing obesity and diabetes; however, the underlying molecular mechanisms are not well elucidated. We aimed to assess whether melatonin has beneficial effects on constant artificial light-induced fat deposition, lipid metabolism, and insulin resistance. Guinea pigs were randomly divided into five experimental groups: control (C), HFD (H), 12 h light (12HL), 24 h light (24HL), and melatonin (M). The majority of indexes, including insulin resistance and obesity, were measured after 10 weeks. AMP-activated protein kinase α (AMPKα)/peroxisome proliferator-activated receptor-α (PPARα) pathway expression was analyzed by quantitative reverse transcription PCR and western blotting. Although insulin resistance and obesity indexes were higher in the 24HL group than in the 12HL group, they were significantly lower in the M group than in the 24HL group. Melatonin treatment markedly upregulated AMPKα, phosphorylated AMPKα (p-AMPKα), PPARα, and carnitine palmitoyl-CoA transferase 1 A (CPT1A) gene and protein expression. Melatonin may alleviate insulin resistance and obesity caused by persistent artificial light exposure in guinea pigs, likely via activation of the AMPKα/PPARα signaling pathway. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a vital hallmark of type 2 diabetes mellitus, which is characterized by an impaired ability of insulin to promote glucose uptake and utilization. Lipid deposition is closely associated with impaired insulin sensitivity. PPARγ plays an important role in glucose homeostasis, adipocyte differentiation, and insulin sensitivity. Likewise, DGAT2 also exerts a crucial role in integrating carbohydrate and lipid metabolism in the liver. The present study is aimed at evaluating a Chinese medicinal formula, Tangduqing granules (TDQ), with multifaceted actions against lipid and glucose metabolism disorder and IR of type 2 diabetes. An animal model of type 2 diabetes was developed by high-fat diet feeding plus low-dose streptozotocin injection. After oral administration of TDQ for 5 weeks, the effects on glucose and lipid metabolism and the underlying mechanism were evaluated by biochemical, histological, RT-PCR, and western blotting methods. The results showed that TDQ decreased fasting blood glucose, ameliorated glucose tolerance, and improved IR. Besides, TDQ regulated hyperlipidemia symptoms, decreased serum lipid levels and liver TG, and reduced hepatic steatosis in a type 2 diabetic rat model. Furthermore, TDQ reversed diabetes-induced decrease in the mRNA and protein expression of PPARγ and elevation in the mRNA and protein levels of DGAT2 in the liver. In addition, we showed that interference of TDQ ameliorated palmitate-induced glucose and lipid metabolic abnormalities in HepG2 cells. TDQ are, therefore, a potential Chinese medicinal formula that relieves IR and lipid metabolism disorder might be through promotion of PPARγ and decrease of DGAT2 expression. [ABSTRACT FROM AUTHOR]

We aimed to clarify how the trajectories of 1-hour postload plasma glucose (PG) and 2-hour PG were different in the development of type 2 diabetes. Using data of repeated health checkups in Japanese workers from April 2006 to March 2016, longitudinal changes of fasting, 1-hour, and 2-hour PG on the oral glucose tolerance test were analyzed with a linear mixed effects model. Of the 1464 nondiabetic subjects at baseline, 112 subjects progressed to type 2 diabetes during the observation period (progressors). In progressors, 1-hour PG and 2-hour PG showed gradual increases with slopes of 1.33 ± 0.2 and 0.58 ± 0.2 mg/dL/year, respectively, followed by a steep increase by which they attained diabetes. Until immediately before the diabetes transition, age- and sex-adjusted mean level of 2-hour PG was 149 ± 2.7 mg/dL, 34 ± 2.7 (30%) higher compared to nonprogressors, while that of 1-hour PG was 206 ± 4.1 mg/dL, 60 ± 4.3 mg/dL (41%) higher compared to nonprogressors. In conclusion, diabetes transition was preceded by a mild elevation of 2-hour PG for several years or more. The elevation in 1-hour PG was larger than that of 2-hour PG until immediately before the transition to diabetes. [ABSTRACT FROM AUTHOR]

Aim. To find the association between biochemical hypoglycemia on a 2-hour screening oral glucose tolerance test (OGTT) and insulin resistance. Method. Subjects of this study were sampled from the China National Diabetes and Metabolic Disorders Study that was conducted during 2007 and 2008. Blood samples were drawn at 0, 30, and 120 minutes after the glucose load. Biochemical hypoglycemia was defined as 2-hour glucose < 3.0 mmol/l. Results. In total, 26,606 participants were included, and 141 participants were diagnosed with biochemical hypoglycemia on a 2-hour OGTT. Compared to participants with normal glucose tolerance (NGT), participants with biochemical hypoglycemia presented with a younger age, lower BMI, lower levels of fasting glucose, and lower levels of 30-minute and 2-hour OGTT glucose. In terms of insulin resistance, participants with biochemical hypoglycemia showed higher levels of Matsuda ISI. In terms of β-cell function, participants with biochemical hypoglycemia showed higher levels of Stumvoll early and late indexes. A multivariate regression analysis indicated that higher levels of Matsuda ISI and higher levels of Stumvoll early and late indexes were associated with biochemical hypoglycemia independently. Conclusion. This study indicated that biochemical hypoglycemia might be associated with lower levels of insulin resistance but higher levels of β-cell function in a Chinese population. [ABSTRACT FROM AUTHOR]

Diabetes in pregnancy contributes to maternal mortality and morbidity though it receives little attention in developing countries. The purpose of the study was to explore the barriers to adherence and possible solutions to nonadherence to antidiabetic therapy in women with diabetes in pregnancy. Antidiabetic therapy referred to diet, physical activity, and medications. Four focus group discussions (FGDs), each with 7 participants, were held at a central hospital in Zimbabwe. Included were women with a diagnosis of diabetes in pregnancy, aged 18 to 49 years, and able to speak Shona or English. Approval was obtained from respective ethical review boards. FGDs followed a semistructured questionnaire. Detailed notes were taken during the interviews which were also being audiotaped. Data were analysed thematically and manually. Themes identified were barriers and possible solutions to nonadherence to therapy. Barriers were poor socioeconomic status, lack of family, peer and community support, effects of pregnancy, complicated therapeutic regimen, pathophysiology of diabetes, cultural and religious beliefs, and poor health care system. Possible solutions were fostering social support, financial support, and improvement of hospital services. Individualised care of women with diabetes is essential, and barriers and possible solutions identified can be utilised to improve care. [ABSTRACT FROM AUTHOR]

In the current study, we developed a liver-specific GGT-overexpressing mice model by rapid injection pLIVE-GGT vector through tail vein and investigated the effects of GGT elevation on glucose metabolism and insulin sensitivity. The serum GGT activity was significantly increased after 7 days of pLIVE-GGT1 vector delivery and lasted for about 3 weeks. GGT overexpression reduced the levels of GSSG and GSH in the liver and serum and had no effects on total antioxidative capacity in the liver, kidney, and skeletal muscle except for the pancreas. Increased GGT activity had no effect on the glucose tolerance but could facilitate blood glucose lowering after intraperitoneal insulin administration. The results of Western blotting showed that increased GGT activity enhanced insulin-induced AKT phosphorylation at Ser473. Furthermore, GGT inhibitor could attenuate the changes of insulin-induced blood glucose uptake and AKT phosphorylation in the liver. In summary, the present study developed a liver-specific GGT-overexpressing mice model and found that GGT elevation in short term had no effects on glucose metabolism but could increase insulin sensitivity through enhancing the activity of insulin signaling pathway. [ABSTRACT FROM AUTHOR]

Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genes in vitro; however, the effects in vivo have not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabetic db/db mice were orally intubated with SA(10 mg kg-1 bodyweight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1. [ABSTRACT FROM AUTHOR]

In China, TianMai Xiaoke tablet (TM) is used to treat type 2 diabetes. However, the exact mechanism of TMis not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML), and high dose of TM group (TMH). Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet. [ABSTRACT FROM AUTHOR]

We investigated the effects of JTT-130 on glucose and lipid metabolism independent of the suppression of feeding by comparing with pair-fed animals. Male Zucker diabetic fatty (ZDF) rats were divided into control, JTT-130 treatment, and pair-fed groups. The rats were fed with a regular powdered diet with or without JTT-130 as a food admixture for 6 weeks.We compared the effects on glucose and lipid metabolism in JTT-130 treatment group with those in pair-fed group. Results. Hyperglycemia in ZDF rats was prevented in both JTT-130 treatment and pair-fed groups, but the prevention in pair-fed group became poor with time. Moreover, reduction in plasma cholesterol levels was observed only in JTT-130 treatment group. JTT-130 treatment group showed improved glucose tolerance at 5 weeks after treatment and significant elevation of portal glucagon-like peptide-1 (GLP-1) levels. The hepatic lipid content in JTT-130 treatment group was decreased as compared with pair-fed group. Furthermore, pancreatic protection effects, such as an increase in pancreatic weight and an elevation of insulin-positive area in islets, were observed after JTT-130 treatment. Conclusions. JTT-130 improves hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake, which is ascribed to an enhancement of GLP-1 secretion and a reduction of lipotoxicity. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 µM, 2 µM, 5 µM, and 10 µM simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 (Cav1.2), and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 µM and 10µM) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P < 0.05). ATP content in simvastatin-treated cells was lower than in control cells (P < 0.05). Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P < 0.05), and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P < 0.05). Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells. [ABSTRACT FROM AUTHOR]

The aim of our case-control study was to compare selected psychological and social characteristics between diabetic patients with and without the DF (controls). Methods. 104 patients with and 48 without DF were included into our study. Both study groups were compared in terms of selected psychosocial characteristics. Results. Compared to controls, patients with DF had a significantly worse quality of life in the area of health and standard of living as shown by lower physical health domain (12.7 ± 2.8 versus 14.7 ± 2.5; P < 0.001) and environment domain (14.1 ± 2.2 versus 15 ± 1.8; P < 0.01) that negatively correlated with diabetes duration (r = -0.061; P = 0.003). Patients with DF subjectively felt more depressed in contrast to controls (24.5 versus 7.3%; P < 0.05); however, the depressive tuning was objectively proven in higher percentage in both study groups (83.2 versus 89.6; NS). We observed a significantly lower level of achieved education (P < 0.01), more patients with disability pensions (P < 0.01), and low self-support (P < 0.001) in patients with the DF compared to controls. In the subgroup of patients with a previous major amputation and DF (n = 6), there were significantly worse outcomes as in the environment domain (P < 0.01), employment status, and stress readaptation (P < 0.01) in contrast to the main study groups. Conclusions. Patients with DF had a predominantly worse standard of living. In contrast to our expectations, patients with DF appeared to have good stress tolerability and mental health (with the exception of patients with previous major amputation) and did not reveal severe forms of depression or any associated consequences. [ABSTRACT FROM AUTHOR]

Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis. [ABSTRACT FROM AUTHOR]

Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome. [ABSTRACT FROM AUTHOR]