Streptozotocin diabetes: A glucoreceptor dysfunction affecting D cells as well as B and A cells

Abstract

Summary. Somatostatin release from the isolated pancreas of 3 normal and 6 streptozotocin diabetic dogs has been measured in response to various stimuli to determine whether abnormalities in somatostatin release are present in the diabetic pancreas. Simultaneous measurement of glucagon secretion was also made. In the pancreas from normal dogs increases in perfusate glucose from 25 to 200mg/100ml induced a 2-3 fold increase in somatostatin release and a two thirds decrease in glucagon secretion. In contrast, in the diabetic pancreas glucose caused no change in the secretion of the two hormones. In the diabetic pancreas addition of insulin to the perfusate (25,000 ~U/ml) for periods from 10 to 75 minutes aimed at restoring normal extracellular insulin levels in the islets failed to restore either somatostatin or glucagon secretion to normal. In contradistinction to the lack of effect of glucose, the somatostatin and glucagon responses to arginine (5 mmol/1), isoproterenol (2 ng/ml) and calcium (5 mmol/1) were normal in the diabetic pancreas. The data suggests the presence of a selective glucoreceptor abnormality of the D as well as of B and A cells in the streptozotocin diabetic dog.

Acute effects of alloxan- and streptozotocin-induced insulin deficiency on somatostatin and glucagon secretion by the perfused isolated rat pancreatico-duodenal preparation

“…If this is correct, it could be argued that the toxic effect of alloxan on insulin secretion removes one regulatory factor from this interaction causing the exaggeration of glucagon release and the decrease of somatostatin release seen in response to arginine and glucose. The failure of insulin infusion after alloxan treatment to influence these responses confirms the data of Hermansen et al [17] and is evidence against this possibility. The use of heterologous insulin in this experiment cannot explain our result in as much as porcine insulin is fully active in the rat.…”

“…Glucagon secretion also increased acutely during alloxan perfusion. Following altoxan the inhibition of glucagon release in response to glucose alone or with theophylline was unchanged, while the response to arginine was exaggerated as previously reported in one similar study [23] but not another utilizing a more chronic preparation [17]. This discrepancy may be explained by the more complete metabolic abnormality seen in long term studies.…”

“…In another study, by contrast, normal pancreatic somatostatin responses to arginine, isoproterenol and calcium and a diminished response to glucose were seen in streptozotocin diabetic dogs [17]. The present study was therefore undertaken to investigate further the acute effects of alloxan and streptozotocin on pancreatic somatostatin secretion in the isolated perfused rat pancreas.…”

Effect of Insulin on Glucose- and Arginine-Stimulated Somatostatin Secretion from the Isolated Perfused Rat Pancreas*

“…The reason for this difference is unclear; apart from the species difference, the composition of the perfusate was also different (20). In the isolated perfused chicken pancreas, Honey and Weir (23) observed a stimulation of somatostatin secretion by 20 mU/ml insulin.…”

“…The increased plasma concentrations of glucagon and somatostatin in dogs with experimental insulinopenic diabetes may suggest an inhibitory action of insulin on the pancreatic a-cells (16) similar to that exerted on the acells (16,17). However, all efforts to demonstrate a direct action of insulin on somatostatin secretion from mammalian pancreas preparations have so far given negative results (6,(18)(19)(20). In the present study, we investigated the effect of insulin on somatostatin release from the isolated perfused rat pancreas under basal conditions and during stimulation with glucose or arginine.…”