Activation of insulin and IGF-1 signaling pathways by melatonin through MT1 receptor in isolated rat pancreatic islets.

Melatonin diminishes insulin release through the activation of MT1 receptors and a reduction in cAMP production in isolated pancreatic islets of neonate and adult rats and in INS-1 cells (an insulin-secreting cell line). The pancreas of pinealectomized rats exhibits degenerative pathological changes with low islet density, indicating that melatonin plays a role to ensure the functioning of pancreatic beta cells. By using immunoprecipitation and immunoblotting analysis we demonstrated, in isolated rat pancreatic islets, that melatonin induces insulin growth factor receptor (IGF-R) and insulin receptor (IR) tyrosine phosphorylation and mediates the activities of the PI3K/AKT and MEK/ERKs pathways, which are involved in cell survival and growth, respectively. Thus, the effects of melatonin on pancreatic islets do not involve a reduction in cAMP levels only. This indoleamine may regulate growth and differentiation of pancreatic islets by activating IGF-I and insulin receptor signaling pathways.

Insulin secretion induced by palmitate--a process fully dependent on glucose concentration.

The effect of 0.1 mM palmitate on insulin secretion by 1 hr incubated pancreatic islets was examined in the presence of different glucose concentrations (5.6 and 16.7 mM). The oxidation of both glucose and palmitate and the incorporation of [U-14C]-palmitate into lipid fractions and phospholipid species were determined. In the presence of 5.6 mM glucose, palmitate reduced insulin release by 80%. In contrast, in the presence of 16.7 mM glucose, palmitate raised the amount of insulin released by 49%. Palmitate (0.1 mM) caused a significant reduction (52%) of [U-14C]-glucose decarboxylation at 5.6 mM but it did not have any effect at 16.7 mM glucose. The decarboxylation of [U-14C]-palmitate was markedly lower (94%) in the presence of 16.7 mM, as compared to 5.6 mM glucose. [U-14C]-Palmitate was significantly incorporated into total lipid fractions in the presence of both glucose concentrations. The increase in glucose concentration from 5.6 to 16.7 mM raised by 138% the incorporation of [U-14C]-palmitate into phospholipids: phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidic acid (PA) and phosphatidylinositol (PI). PC and PA at 0.1 mM raised by three and four-fold, respectively, insulin release by incubated pancreatic islets. We postulated that palmitate (at 0.1 mM) promotes a deviation of glycerol-phosphate to lipid synthesis, decreasing glucose oxidation (at 5.6 mM) and possibly ATP/ADP ratio in the cytosol, leading to a reduction in insulin secretion. At 16.7 mM glucose concentration, the high glycolytic flux is now enough to provide glycerol-phosphate for lipid synthesis and carbons for the Krebs cycle. So, under this condition, ATP production might be not reduced. The increase in the production of PA and PC may explain the increase in insulin secretion observed at 16.7 mM glucose.

Tolerable dietary lipid content that does not alter insulin secretion.

Lipids, either as membrane components or as fuel, are important nutrients that can affect insulin secretion. The aim of this study was to establish the maximum tolerable amount of fat present in the diet, which does not induce significant alteration in the process of insulin secretion. For that, just-weaned male albino rats (70-90 g body weight) were fed during 6 weeks with diets for growing rodents containing 7% fat (A Group) as recommended by the American Institute of Nutrition-AIN. Two other groups in which the fat content of the diet was increased to reach 10% (B Group) or 13% (C Group) were also included. Insulin release, 86Rb+ and 45Ca2+ Fractional Outflow Rate (FOR) during the process of glucose-induced insulin secretion was determined in perfused islets isolated from these animals. No statistical differences in these parameters were detected between A and B rats. However, in the C group, a lower 86Rb+ FOR was found during the whole experiment and a poor insulin secretory response to glucose stimulus was observed. These results led us to postulate that the maximal limiting amount of total lipids present in the diet that does not impair the process of glucose-induced insulin secretion is 10%. These findings authorize future studies on the interference of different dietary lipid sources, in a content 43% more elevated than that recommended (10% against 7%), on the mechanisms of insulin secretion.

Soybean- and olive-oils-enriched diets increase insulin secretion to glucose stimulus in isolated pancreatic rat islets.

Islets isolated from rats fed a lipid-enriched diet have shown an impairment of insulin secretion, but there is no available data comparing the effect of diet containing different dietary fat. This may be important in preventing or facilitating the establishment of diabetes. In this study, the effect of diets enriched (10%) with different fatty acids on insulin secretion by isolated pancreatic islets was investigated. The sources of the fatty acids tested were: saturated long chain from animal fat (AF), polyunsaturated from soybean oil (SO), and monounsaturated from olive oil (OL). The results were compared with those from rats receiving a diet enriched (10%) with a balanced mixture of fatty acids (the same proportion of AF, SO, and OL). The effect of fat-rich diets on insulin release was tested in vivo by giving a glucose load (glucose tolerance test-GTT) and in vitro in perfused islets. The mechanism involved was also examined by measuring 45Ca2+ and 86Rb+ fluxes, GLUT-2 content, and glucose oxidation in isolated islets. A significant increase of insulin secretion and glucose oxidation without any alteration of the ionic movements were detected in islets from SO and OL rats. GLUT-2 content was increased in islets of the OL group but diminished in AF rats. The results led us to postulate that soybean and olive oils may increase the response of insulin secretion to glucose stimulus in pancreatic islets.