Islets Of Rat Pancreas Research Articles

Inhibition of insulin release by synthetic rat C-peptide II in isolated rat islets.

The effect of synthetic rat C-peptide on glucose-induced insulin release was studied in isolated islets of rat pancreas. Addition of rat C-peptide II to the medium inhibited glucose-induced insulin release from islets by 30 to 40 percent. Rat C-peptide I, human connecting peptide and bovine, porcine and canine C-peptides had no significant effects on insulin release from islets of rat pancreas.

Effects of mannoheptulose and DL-glyceraldehyde on glucose induced insulin release and adenosine 3',5'-monophosphate levels in isolated islets of rat pancreas.

The effects of mannoheptulose and DL-glyceraldehyde on glucose-induced insulin release and cycli AMP levels in islets isolated from rat pancreas were investigated. Mannoheptulose inhibition on glucose-induced insulin release was observed after only 5-min incubation period, indicating an inhibitory effect on the early phase of insulin release. This inhibition on insulin release was accompanied with the simultaneous depression of cyclic AMP levels in islets. By the addition of DL-glyceraldehyde to the medium in which glucose and mannoheptulose were present, the depressed cyclic AMP levels in islets were recovered to the control level completely but the restoration of insulin release in the early phase was not complete. In the absence of glucose, DL-glyceraldehyde did not demonstrate a significant increase of insulin release during 5 min incubation, though a marked stimulation was observed after 30-min incubation. Cyclic AMP levels in islets were not affected by DL-glyceraldehyde. When DL-glyceraldehyde was added to the medium with glucose, significant inhibition of glucos-induced insulin release in its early phase was observed without the reduction of cyclic AMP levels in islets. From these findings, the following possibilities are suggested and discussed. 1. Maintenance of the cyclic AMP levels in islets is a necessary but insufficient condition for glucose-induced insulin release particularly for its early phase. 2. Glucose-induced insulin release seems to depend on both the binding of glucose with glucoreceptor and the supply of some metabolites. Mannoheptulose inhibits both mechanisms. DL-glyceraldehyde may supply metabolites but competitively inhibit the binding of glucose to the glucoreceptor.

(Pro‐)Insulin Biosynthesis and Release of Newly Synthesized (Pro‐)Insulin from Isolated Islets of Rat Pancreas in the Presence of Amino Acids and Sulphonylureas+,++

Abstract. The influence of arginine, lysine, tolbutamide and glibenclamide on (pro‐)insulin biosynthesis and release of newly synthesized (pro‐)insulin was studied in isolated islets of rat pancreas. Islets were incubated with 3H‐leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four test substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro‐)insulin was found. Arginine and tolbutamide even markedly reduced (pro‐)insulin synthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro‐)insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca++. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro‐)insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro‐)insulin was observed during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no signifcant changes were found in the specific radioactivity of released (pro‐)insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro‐) insulin when labelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.

(Pro-) insulin biosynthesis and release of newly synthesized (pro-) insulin from isolated islets of rat pancreas in the presence of amino acids and sulphonylureas.

The influence of arginine, lysine, tolbutamide and glibenclamide on (pro-) insulin biosynthesis and release of newly synthesized (pro-) insulin was studied in isolated islets of rat pancreas. Islets were incubated with 3H-leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro-) insulin was found. Arginine and tolbutamide even markedly reduced (pro-) insulin aynthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro-) insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca++. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro-) insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro-) insulin was obsevered during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no significant changes were found in the specific radioactivity of released (pro-) insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro-)insulin when lebelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.

Somatostatin-Induced Inhibition of Insulin Secretion from Isolated Islets of Rat Pancreas in Presence of Glucagon

In order to study the oeffect of somatostatin on the endocrine pancreas directly, islets isolated from rat pancreas by collagenase were incubated for 2 hrs 1) at 50 and 200 mg/100 ml glucose in the absence and presence of somatostatin (1, 10 and 100 mg/ml) and2) at 200 mg/100 ml glucose together with glucagon (5 mug/ml), with or without somatostatin (100 ng/ml). Immunologically measurable insulin was determined in the incubation media at 0, 1 and 2 hrs. Insulin release was not statistically affected by any concentration stomatostatin. On the other hand, somatostatin exerted a significant inhibitory action on glucagon-potentiated insulin secretion (mean +/- SEM, mu1/2 hrs/10 islets: glucose and glucagon: 1253 +/- 92; glucose, glucagon and somatostatin: 786 +/- 76). The insulin output in th epresence of glucose, glucagon and somatostatin was also significantly smaller than in thepresence of glucose alone (1104 +/- 126) or of glucose and somatostatin (1061 +/- 122). The failure of somatostatin to affect glucose-stimulated release of insulin from isolated islets contrasts its inhibitory action on insulin secretion as observed in the isolated perfused pancreas and in vivo. This discrepancy might be ascribed to the isolation procedure using collagenase. However, somatostatin inhibited glucagon-potentiated insulin secretion in isolated islets which resulted in even lower insulin levels than obtained in the parallel experiments without glucagon. It is concluded that the hormone of the alpha cells, or the cyclic AMP system, might play a part in the machanism of somatostatin-induced inhibition of insulin release from the beta-cell.

Regulation by various hormones and agents of adenosine-3′,5′-monophosphate levels in islets of langerhans of rats

Regulation by various hormones and agents of adenosine-3′,5′-monophosphatc (cyclic AMP) levels in intact islets of rat pancreas was studied, employing either the prelabeling technique or the protein kinase catalytic method. Many agents were found to increase islet cyclic AMP levels. These include corticotropin, glucagon, isoproterenol, prostaglandins (E 1, E 2, A 1, and F 1), secretin, thyroid-stimulating hormone, β-adrencrgic agonists, tolbutamide and GTP. Epinephrine caused a slight decrease in islet cyclic AMP level, but in the presence of z-adrenergic blockers, they conversely increased the cyclic AMP levels. Isoproterenol, on the other hand, increased cyclic AMP levels and its effect was abolished by β-adrenergic blocking agents. The evidence presented further substantiates the contention that in rat islet plasma membranes there exist both α- and β-ardenergic receptors and that cyclic AMP levels in islets are closely modulated by α- and β-adrenergic receptor activation.

The role of the exocrine pancreas in the stimulation of insulin secretion by intestinal hormones. I. The effect of pancreozymin, secretin, gastrin-pentapeptide and of glucagon upon insulin secretion of isolated islets of rat pancreas.

The role of the exocrine pancreas in the stimulation of insulin secretion by intestinal hormones. I. The effect of pancreozymin, secretin, gastrin-pentapeptide and of glucagon upon insulin secretion of isolated islets of rat pancreas.