Immediate and delayed effects of D-fructose upon insulin, somatostatin, and glucagon release by the perfused rat pancreas.

Novel information was recently provided concerning the reciprocal effects of D-glucose and D-fructose upon their respective metabolism in rat pancreatic islets. In the light of such findings, this study aims at comparing the effects of D-glucose and D-fructose on insulin, somatostatin, and glucagon release from the isolated perfused rat pancreas. A rise in D-glucose concentration from 3.

Assessment of islet beta-cell mass in isolated rat pancreases perfused with D-[(3)H]mannoheptulose.

D-mannoheptulose is apparently transported into cells mainly at the intervention of GLUT-2 and hence was recently proposed as a tool to label preferentially insulin-producing beta-cells in the pancreatic gland. The validity of such a proposal was investigated in the present study conducted in isolated perfused pancreatic glands from control and streptozotocin-induced diabetic rats. After a 30-min equilibration period, D-[(3)H]mannoheptulose (0.

Effects of D-mannoheptulose and its hexaacetate ester on hormonal secretion from the perfused pancreas.

D-mannoheptulose was recently proposed to be transported into cells by GLUT2, whereas its hexaacetate ester may cross the plasma membrane without requiring the intervention of a specific carrier system. In the light of these proposals, the effects of unesterified D-mannoheptulose and D-mannoheptulose hexaacetate upon hormonal secretion by the perfused rat pancreas were now investigated. Unesterified D-mannoheptulose (1.

Stimulation by 2-deoxy-D-glucose tetraacetates of hormonal secretion from the perfused rat pancreas.

The effects of alpha- and beta-2-deoxy-D-glucose tetraacetate (1.7 and 8.5 mM) on insulin, somatostatin, and glucagon secretion from isolated rat pancreases perfused in the presence of 8.

Dual mode of action of glucose pentaacetates on hormonal secretion from the isolated perfused rat pancreas.

Isolated perfused rat pancreases were exposed, in the presence of 10. 0 mM L-leucine, to either alpha-D-glucose pentaacetate, beta-L-glucose pentaacetate, or unesterified D-glucose, all tested at a 1.7 mM concentration.

GLP-1 receptors in golden Syrian hamster islets: identification and functional characterization.

This study aims at the identification and functional characterization of glucagon-like peptide 1 (7-36) amide (GLP-1) receptor in islets from Golden Syrian hamsters. Using a polyclonal antibody against rat GLP-1 receptors, Western blotting of the islet proteins revealed two major bands of 44 and 70 kDa, similar to those found in rat islets, RINm5F cells, and HIT-T15 cells. In Northern blots, transcripts of 2.

Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration.

In isolated perfused pancreas from normal rats, a rise in d-glucose concentration from 3.3 to 8.3 mM provoked a rapid phasic stimulation of both insulin and somatostatin secretion and rapid fall in glucagon output, these changes being reversed when the concentration of the hexose was brought back to its initial low level.

Stimulation of insulin and somatostatin release by two meglitinide analogs.

Several meglitinide analogs are currently under investigation as potential insulinotropic tools for the treatment of noninsulin-dependent diabetes. The present study aimed to further insight into the effect of these agents on the secretion of insulin, glucagon, and somatostatin by the isolated perfused pancreas. Both repaglinide (0.

Modulation of gliquidone action by forskolin in the pancreas of normal and GK rats.

This study aims to investigate whether agents that stimulate adenosine 3',5'-cyclic monophosphate (cAMP) formation could be used to increase insulin release evoked by hypoglycemic sulfonylureas in non-insulin-dependent diabetes mellitus. For this purpose, the effect of gliquidone (1.0 microM) on insulin and glucagon release was examined in the perfused pancreas of either normal or Goto-Kakizaki (GK) rats at a low concentration of D-glucose (2.

Effect of C-peptide on insulin and glucagon release by isolated perfused rat pancreas.

Administration of rat C-peptide (0.1 mumol/l) to isolated rat pancrease failed to inhibit insulin release induced by a high concentration of D-glucose (11.1 mmol/l) but prevented the progressive increase in insulin output otherwise observed during prolonged perfusion in the presence of 3.

Do leptin receptors play a functional role in the endocrine pancreas?

It was recently speculated that leptin may exert a direct inhibitory effect upon insulin release from the pancreatic B-cell. This proposal meets, however, with two objections. First, although the message for leptin receptors is indeed detected in rat pancreatic islets, the short form of this receptor, for which no signalling function is known, represents the major species present in islet cells.

Potentiation of GLP-1 insulinotropic action by a nonglucidic nutrient in the pancreas of diabetic GK rats.

Glucagon-like peptide 1 (GLP-1) is often referred to as a glucose-dependent insulinotropic agent and is currently under investigation as a tool in the treatment of noninsulin-dependent diabetes. This report shows that, in the absence of glucose, a nonglucidic nutrient, namely succinic acid dimethyl ester (SAD), allows full expression of the insulinotropic potential of GLP-1 in the perfused pancreas from diabetic GK rats. Thus, whereas the insulin and glucagon responses to GLP-1 in GK rats differ from those previously documented in nondiabetic animals when tested in the absence of exogenous nutrient, the secretory response of the endocrine pancreas to GLP-1 is virtually normalized in the GK rats when SAD is incorporated into the perfusate.

Relevance of lactate dehydrogenase activity to the control of oxidative glycolysis in pancreatic islet B-cells.

The activities of hexokinase isoenzymes, lactate dehydrogenase, cytosolic NAD-linked glycerophosphate dehydrogenase, mitochondrial FAD-linked glycerophosphate dehydrogenase, and glutamate dehydrogenase were measured in homogenates of rat purified pancreatic B and non-B islet cells. In B cell homogenates, the maximal activity of hexokinase and glucokinase was one to two orders of magnitude lower than that of lactate dehydrogenase. The activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase was also much lower than that of the cytosolic NAD-linked glycerophosphate dehydrogenase .

Potentiation of glucagon-like peptide 1 insulinotropic action by succinic acid dimethyl ester.

The glucagon-like peptide 1 (7-36) amide (GLP-1, 1.0 nM) was administered to isolated rat pancreases perfused either in the absence of exogenous nutrient or presence of 10 mM succinic acid dimethyl ester (SAD). In the absence of any exogenous nutrient, GLP-1 failed to affect either insulin or glucagon release.

In vitro and in vivo insulinotropic action of methyl pyruvate.

Methyl pyruvate, when tested at a 10mM concentration, caused a rapid and sustained increase of insulin release evoked by either 7.0 or 16.7 mM D-glucose in the isolated perfused rat pancreas.

Restricted effect of formycin A and non-glucidic nutrients upon insulin release in islets from rats with hereditary or acquired non-insulin-dependent diabetes.

Pancreatic islets isolated from control rats, Goto-Kakizaki rats and adult rats that were injected with streptozotocin during the neonatal period were incubated for two successive period of 90 min each in the presence of D-glucose (11.1 mM) with or without formycin A (1.0 mM), and in the presence of the dimethyl ester of succinic acid (SAD, 10.

Insulinotropic action of glutamic acid dimethyl ester.

Glutamic acid dimethyl ester (GME; 3.0-10.0 mM) enhanced insulin release evoked by 6.

Pancreatic islet response to dicarboxylic acid esters in rats with type 2 diabetes: enzymatic, metabolic and secretory aspects.

This study aimed to compare the metabolic and secretory responses of pancreatic islets from animals with non-insulin-dependent diabetes to D-glucose with the effects of the methyl esters of succinic acid (SME) and glutamic acid (GME). The insulin secretory response to D-glucose was impaired in islets from rats with diabetes which was either inherited (Goto-Kakizaki (GK) rats) or acquired (streptozotocin-treated (STZ) rats). This coincided with a preferential alteration of oxidative relative to total glycolysis in intact islets and a selective defect of FAD-linked mitochondrial glycerophosphate dehydrogenase (m-GDH) in islet homogenates.

Impaired FAD-glycerophosphate dehydrogenase activity in islet and liver homogenates of fa/fa rats.

The mitochondrial FAD-linked enzyme glycerophosphate dehydrogenase plays a key role in the pancreatic B-cell glucose sensing device. In the present study, the activity of this enzyme was examined in islets of fa/fa rats in which inherited diabetes mellitus is associated with obesity, hyperinsulinism and severe insulin resistance. The specific activity of both FAD-linked glycerophosphate dehydrogenase and glutamate dehydrogenase were decreased in islet and liver homogenates prepared from fa/fa, as compared to Fa/Fa, rats, this coinciding with a low ratio between glutamateoxalacetate and glutamate-pyruvate transaminase activity in both islet and liver extracts, islet hyperplasia, hyperinsulinemia and hepatic steatosis in the hyperglycemic fa/fa rats.

Enhancement by succinic acid dimethyl ester of insulin release evoked by D-glucose and glimepiride in the perfused pancreas of normoglycemic and hyperglycemic rats.

The present study deals with the insulinotropic action of the dimethyl ester of succinic acid (SAD), considered as a potential tool for the treatment of non-insulin-dependent diabetes mellitus. In the perfused pancreas prepared from either euglycemic rats or animals first infused for 48 hours with a solution of D-glucose, SAD (10 mM) markedly enhanced insulin output evoked by a high concentration of D-glucose (16.7 mM), whether in the absence or presence of glimepiride (0.

Secretory, biosynthetic, respiratory, cationic, and metabolic responses of pancreatic islets to palmitate and oleate.

Palmitate and oleate (0.5 to 1.0 mM) caused a time- and concentration-related augmentation of insulin release evoked by D-glucose (6.

In vivo stimulation of insulin release by succinic acid methyl esters.

Both the monomethyl and dimethyl esters of succinic acid, administered intravenously to fasted and anesthetized rats, caused a rapid increase in plasma insulin. A positive insulin secretory response to succinic acid monomethyl ester was also observed after intraperitoneal injection to fed and conscious rats. On a molar basis, stimulation of the insulin release, evoked by succinic acid esters, represented about twice that caused by D-glucose.

Insulinotropic action of the D-glucosyl and 3-O-methyl-D-glucosyl monomethyl esters of succinic acid.

Succinic acid methyl esters are currently under investigation as potential insulinotropic tools in animal models of non-insulin-dependent diabetes mellitus. The in vivo administration of these esters may result in the undesirable generation of methanol through their intracellular hydrolysis. As a first attempt to circumvert this drawback, we have now investigated whether the esterification of the carboxylic group of succinic acid monomethyl ester by D-glucose or 3-O-methyl-D-glucose affects its insulin-otropic action.

Metabolic, ionic, and secretory response to D-glucose in islets from rats with acquired or inherited non-insulin-dependent diabetes.

The metabolic, ionic, and secretory response to D-glucose was investigated in islets of adult rats either injected with streptozotocin during the neonatal period (STZ rats) or presenting with inherited diabetes (GK rats). At a high concentration of D-glucose (16.7 mM), the ATP/ADP ratio was lower in islets from STZ and GK than control rats.

FAD-linked glycerophosphate dehydrogenase activity in islets, liver, and splenocytes of NOD mice.

The activity of FAD-linked glycerophosphate dehydrogenase (m-GDH), as well as that of glutamate dehydrogenase and both glutamate-oxalacetate and glutamate-pyruvate transaminases, were measured in islet, liver, and splenocyte homogenates from 6- to 7-week-old female nonobese diabetic mice (NOD) and age- and sex-matched control mice. Despite incipient insulitis and euglycemia, the NOD mice displayed both high islet insulin content and elevated insulinemia. The activity of m-GDH, expressed relative to protein content, was not decreased in islets of NOD mice, despite the fact that such a specific activity is lower in splenic lymphocytes than islet cells.