Search

Taurine (TAU) supplementation increases insulin secretion in response to high glucose concentrations in rodent islets. This effect is probably due to an increase in Ca2+ handling by the islet cells. Here, we investigated the possible involvement of the cholinergic/phospholipase C (PLC) and protein kinase (PK) A pathways in this process. Adult mice were fed with 2 % TAU in drinking water for 30 d. The mice were killed and pancreatic islets isolated by the collagenase method. Islets from TAU-supplemented mice showed higher insulin secretion in the presence of 8·3 mm-glucose, 100 μm-carbachol (Cch) and 1 mm-3-isobutyl-1-methyl-xanthine (IBMX), respectively. The increase in insulin secretion in response to Cch in TAU islets was accompanied by a higher intracellular Ca2+ mobilisation and PLCβ2 protein expression. The Ca2+ uptake was higher in TAU islets in the presence of 8·3 mm-glucose, but similar when the islets were challenged by glucose plus IBMX. TAU islets also showed an increase in the expression of PKAα protein. This protein may play a role in cation accumulation, since the amount of Ca2+ in these islets was significantly reduced by the PKA inhibitors: N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H89) and PK inhibitor-(6–22)-amide (PKI). In conclusion, TAU supplementation increases insulin secretion in response to glucose, favouring both influx and internal mobilisation of Ca2+, and these effects seem to involve the activation of both PLC–inositol-1,4,5-trisphosphate and cAMP–PKA pathways. [ABSTRACT FROM PUBLISHER]

The article discusses research on the levels of plasma insulin and the Phosphoenolpyruvate (P-enolpyruvate) carboxykinase (PEPCK) activity in common vampire bats. The subjects of the study were male and non-pregrant female bats for determining the effects of feeding on PEPCK activity in bats. The study found the low resistance of bats to fasting that hypoglycemia develops after 12 hours of fasting. The study also revealed that the cytoplasmic activity of PEPCK among vampire bats is 400% higher among those that have not been fed than those that are fed.

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease's (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent characterization of the ability of uncoupling protein 2 (UCP2) to reduce ATP production and inhibit insulin secretion by pancreatic β-cells has placed this mitochondrial protein as a candidate target for therapeutics in diabetes mellitus. In the present study we evaluate the effects of short-term treatment of two animal models of type 2 diabetes mellitus with an antisense oligonucleotide to UCP2. In both models, Swiss mice (made obese and diabetic by a hyperlipidic diet) and ob/ob mice, the treatment resulted in a significant improvement in the hyperglycemic syndrome. This effect was due not only to an improvement of insulin secretion, but also to improved peripheral insulin action. In isolated pancreatic islets, the partial inhibition of UCP2 increased ATP content, followed by increased glucose-stimulated insulin secretion. This was not accompanied by increased expression of enzymes involved in protection against oxidative stress. The evaluation of insulin action in peripheral tissues revealed that the inhibition of UCP2 expression significantly improved insulin signal transduction in adipose tissue. In conclusion, short-term inhibition of UCP2 expression ameliorates the hyperglycemic syndrome in two distinct animal models of obesity and diabetes. Metabolic improvement is due to a combined effect on insulin-producing pancreatic islets and in at least one peripheral tissue that acts as a target for insulin. [ABSTRACT FROM AUTHOR]

The serum mineral levels, glucose disappearance rate (kg), total area under the glucose (??G) and insulin (??I) curves, and static insulin secretion were compared among rats fed a Mg-deficient diet for 6 (DF-6) or 11 (DF-11) weeks, and rats fed a control diet for the same periods (CO-6 and CO-11 groups). No change in glucose homeostasis was observed among DF-6, CO-6 and CO-11 rats. DF-11 rats showed an elevated kg and a reduced ??G and ??I. For evaluating the effect of supplementation, rats fed a control or Mg-deficient diet for 6 weeks were then fed a Mg- supplemented diet for 5 weeks (SCO and SDF groups respectively). The serum Mg levels in SDF rats were similar to those in CO-11 and SCO rats, but higher than in the DF-11 group. SDF rats showed similar kg, ??G and ??I compared with the CO-11 and SCO groups. However, a significantly lower kg and higher ??G and ??I were observed in SDF compared with DF-11 rats. Basal and 8.3 mmol glucose/l-stimulated insulin secretion by islets from DF-11 rats were higher than by islets from CO-11 rats. These results indicate that moderate Mg depletion for a long period may increase the secretion and sensitivity to insulin, while Mg supplementation in formerly Mg-deficient rats may prevent the increase in sensitivity and secretion of insulin. [ABSTRACT FROM PUBLISHER]

1. The effects of glucose on insulin secretion and 86Rb efflux from isolated rat islets were studied at six different times during a 24-h period (00.00, 04.00, 08.00, 12.00, 16.00 and 20.00 h). 2. In the absence of glucose and in the presence of substimulatory concentrations (2.8 mmol/L) of the sugar, insulin secretion did not vary with the time of day. At a glucose concentration of 5.6 mmol/L the stimulated insulin secretion was greater than basal levels only at 20.00 h. 3. At a higher sugar concentration (8.3 mmol/L) the increase in insulin secretion and the reduction in 86Rb efflux rate were more marked during the dark period. No effect of the time of day on insulin secretion was observed at glucose concentrations above 8.3 mmol/L (except in 27.7 mmol/L). 4. The time of day appears to affect insulin secretion mainly at glucose concentrations close to physiological values (5.6–8.3 mmol/L). 5. This result agrees with the ability of physiological amounts of glucose to alter the 86Rb-permeability of pancreatic B cells at the same time intervals. [ABSTRACT FROM AUTHOR]

Maternal malnutrition was shown to affect early growth and leads to permanent alterations in insulin secretion and sensitivity of offspring. In addition, epidemiological studies showed an association between low birth weight and glucose intolerance in adult life. To understand these interactions better, we investigated the insulin secretion by isolated islets and the early events related to insulin action in the hind-limb muscle of adult rats fed a diet of 17% protein (control) or 6% protein [low (LP) protein] during fetal life, suckling and after weaning, and in rats receiving 6% protein during fetal life and suckling followed by a 17% protein diet after weaning (recovered). The basal and maximal insulin secretion by islets from rats fed LP diet and the basal release by islets from recovered rats were significantly lower than that of control rats. The dose-response curves to glucose of islets from LP and recovered groups were shifted to the right compared to control islets, with the half-maximal response (EC50) occurring at 16.9 +/- 1.3, 12.4 +/- 0.5 and 8.4 +/- 0.1 mmol/L, respectively. The levels of insulin receptor, as well as insulin receptor substrate-1 and phosphorylation and the association between insulin receptor substrate-1 and phosphatidylinositol 3-kinase were greater in rats fed a LP diet than in control rats. In recovered rats, these variables were not significantly different from those of the other two groups. These results suggest that glucose homeostasis is maintained in LP and recovered rats by an increased sensitivity to insulin as a result of alterations in the early steps of the insulin signal transduction pathway. [ABSTRACT FROM AUTHOR]

The effects of the muscarinic agonist oxotremorine-m (oxo-m) on insulin secretion, K(+)-permeability and electrical activity from isolated mouse pancreatic islets were studied. Oxo-m potentiated glucose-induced insulin secretion in a dose-dependent manner, saturating at ca. 10 microM. At 11.2 mM glucose, oxo-m (0.1 and 10 microM) had two distinct effects on beta-cell electrical activity. Both concentrations increased the steady-state burst frequency, however, at 10 microM an initial and transient polarization was measured, and the subsequent activity was accompanied by a slight depolarization. The polarizing effect of oxo-m was almost completely suppressed by charybdotoxin (ChTX), a blocker of the large conductance (maxi) [Ca2+]i-activated potassium channel (K(Ca)). In the presence of 11.2 mM glucose, oxo-m (50 microM) provoked a significant and transient increase in the 86Rb efflux from perifused islets. This effect was inhibited by ChTX. ChTX also potentiated oxo-m stimulated insulin secretion in the presence of glucose. Finally, the balance between the polarizing and depolarizing effects of oxo-m was variable in different islets and depended on glucose concentration. Insulin secretion stimulated by oxo-m in the presence of glucose was more closely correlated to the agonist induced increase in burst frequency than to an increase in plateau fraction. We conclude that muscarinic stimulation has at least two effects on beta-cell electrical activity, an initial hyperpolarization, owing to activation of K(Ca) channels, followed by depolarization and high-frequency bursts, proposed to reflect the activation of a current sensitive to the depletion of intracellular Ca2+ stores (CRAC). [ABSTRACT FROM AUTHOR]

Islet amyloid polypeptide (IAPP or amylin) is a hormone co‐secreted with insulin by pancreatic β‐cells and is the major component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes (T2D) and may be involved in β‐cell dysfunction and death, observed in this disease. Thus, investigating the aspects related to amyloid formation is relevant to the development of strategies towards β‐cell protection. In this sense, IAPP misprocessing, IAPP overproduction, and disturbances in intra‐ and extracellular environments seem to be decisive for IAPP to form islet amyloid. Islet amyloid toxicity in β‐cells may be triggered in intra‐ and/or extracellular sites by membrane damage, endoplasmic reticulum stress, autophagy disruption, mitochondrial dysfunction, inflammation, and apoptosis. Importantly, different approaches have been suggested to prevent islet amyloid cytotoxicity, from inhibition of IAPP aggregation to attenuation of cell death mechanisms. Such approaches have improved β‐cell function and prevented the development of hyperglycemia in animals. Therefore, counteracting islet amyloid may be a promising therapy for T2D treatment. [ABSTRACT FROM AUTHOR]

Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml−1, increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM. [ABSTRACT FROM AUTHOR]

We studied the transcription and immunocytochemical presence of Islet Neogenesis-Associated Protein (INGAP) and measured the binding in vivo of [sup 125]I-tyrosylated INGAP pentadecapeptide ([sup 125]I-T-INGAP-PP) to different normal male hamster tissues. INGAP transcription (RT-PCR) and immunocytochemical expression (INGAP-positive cells) were assessed in hamster tissues. I[sup 125]-T-INGAP-PP with our without T-INGAP-PP (0-1 mg/100 g bw) was injected and blood samples were drawn 5 and 60 min after injection. Radioactivity was measured in serum, brain, liver, kidney, small intestine, striated muscle, dorsal root ganglia and pancreas; results were expressed as the organ/serum ratio. We identified INGAP-positive cells and mRNA only in pancreatic islets and exocrine tissue. Radioactivity in serum samples increased from 0 (1,952 cpm/g serum) to 60 min (36,566 cpm/g serum). The simultaneous administration of T-INGAP-PP decreased this activity by 71% at 5, 10 and 20 min, but only by 9% at 60 min. Liver, pancreas and small intestine showed specific binding for 12H-T-INGAP-PP; the 50% displacement obtained with a 39.10² ng dose of T-INGAP-PP/100 g bw suggests the presence of a pancreatic receptor with low affinity for this peptide. We can conclude that INGAP transcription/expression is probably restricted to the pancreas where it would exert its effect in a paracrine fashion. INGAP would be released and circulate bound to a serum protein, and would bind to the liver for subsequent inactivation. INGAP binding to the small intestine would explain its immunocythochemical presence in this organ, where it would play a key role in the regulation of epithelial cell turnover. [ABSTRACT FROM AUTHOR]