Effects of islet hormones on insulin secretion from cloned B cell lines, HIT-T15 and RINm5F

ABSTRACT The effects of the islet cell hormones glucagon, somatostatin-28 and pancreatic polypeptide on insulin secretion from cultured cloned pancreatic B cells (HIT-T15 and RINm5F) have been investigated. Glucagon stimulates the secretion of insulin from HIT-T15 cells in the absence and presence of glucose and from RINm5F cells in the absence and presence of glyceraldehyde. HIT-T15 cells were more sensitive to the stimulatory effect of glucagon than RINm5F cells. Somatostatin-28 and pancreatic polypeptide, both alone and in combination, reduced glucose- and glucagon-stimulated insulin release from HIT-T15 cells and glyceraldehyde- and glucagon-stimulated insulin release from RINm5F cells. HIT-T15 cells were more sensitive to the inhibitory actions of somatostatin-28 and pancreatic polypeptide than RINm5F cells. This study supports the hypothesis that insulin release from normal B cells may be modified by the paracrine activity of islet hormones, glucagon, somatostatin and pancreatic polypeptide and probably occurs before any fine tuning imposed by subsequently released insulin. Journal of Endocrinology (1989) 121, 479–485

Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly

Ten acromegalic patients, 28–71 years old, were compared with 10 normal controls, 21–39 years old. In another study, 7 patients with active acromegaly, 19–70 years old, were investigated before and 4–9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF)) was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 ± 3.8 and 16.6 ± 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 ± 23.9 and 63 ± 11.8 mU/1, respectively) and lower plasma glucagon (peak values 171 ± 29.0 and 310 ± 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 ± 2.6 and 15.2 ± 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 ± 38.8 and 91 ± 24.9 mU/1, respectively). Plasma glucagon was similar before and after the operation (peak values 143 ± 23.4 and 127 ± 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.

Regulation of digestion. II. Effects of insulin and glucagon on pancreatic secretion

The endocrine islet-cell hormones insulin and glucagon are secreted at high concentrations into an intrapancreatic portal circulation and have been reported to affect the secretion of digestive enzyme by the exocrine pancreas. In the present experiments, insulin and glucagon were injected into the celiac artery of anesthetized rats to evaluate their effects on the secretion of amylase and trypsinogen by the pancreas. Neither hormone when given alone significantly changed the output of either enzyme. However, when given with the pancreatic secretagogue cholecystokinin, each altered the effect of injection of cholecystokinin. In a dose-dependent fashion insulin increased trypsinogen output without affecting amylase output, whereas glucagon inhibited amylase output and left trypsinogen output unchanged. Thus, both hormones produced a more trypsinogen-dominant pancreatic juice than that observed with cholecystokinin alone, although in different ways. These findings suggest that the endocrine hormones insulin and glucagon may regulate secretion of digestive enzymes by the pancreas by modulating the response to stimuli of overall protein secretion such as cholecystokinin.