Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin

Abstract

Aims/hypothesis Somatostatin from islet delta cells inhibits insulin and glucagon secretion, but knowledge of the regulation of pancreatic somatostatin release is limited. Some insulin secretagogues stimulate somatostatin secretion, and here we investigated whether delta cell secretory responses are indirectly regulated in a paracrine manner by insulin released from beta cells. Methods Hormone release from static incubations of primary mouse islets or somatostatin-secreting TGP52 cells was measured by RIA. mRNA expression was assessed by RT-PCR. Results Glucose and a range of other physiological and pharmacological agents stimulated insulin and somatostatin release, and insulin receptor mRNA was expressed in islets, MIN6 beta cells and TGP52 cells. However, exogenous insulin did not modulate basal or glucose-induced somatostatin secretion from islets, nor did pre-incubation with an antibody against the insulin receptor or with the insulin receptor tyrosine kinase inhibitor, HNMPA(AM) 3 . Glucose and tolbutamide stimulated somatostatin release from TGP52 cells, whereas a range of receptor-operating agents had no effect, the latter being consistent with a lack of corresponding receptor mRNA expression in these cells. Parasympathetic activation stimulated insulin, but inhibited somatostatin release from mouse islets in accordance with differences in muscarinic receptor mRNA expression in islets, MIN6 and TGP52 cells. The inhibitory effect on somatostatin secretion was reversed by pertussis toxin or the muscarinic receptor 2 antagonist, methoctramine. Conclusions/interpretations A number of insulin secretagogues have analogous effects on insulin and somatostatin release, but this similarity of response is not mediated by an indirect, paracrine action of insulin on delta cells.

GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans

“…These data are consistent with a substantial body of earlier work [29–39]. In addition, we observed that the muscarinic cholinergic agonist CCh inhibited glucose-induced somatostatin secretion, in accord with Hauge-Evans et al [33, 34]. Importantly, it should be noted that muscarinic cholinergic receptor isoforms are expressed differentially in beta and delta cells and, as a consequence, their responses to parasympathetic stimulation are different.…”

“…Importantly, it should be noted that muscarinic cholinergic receptor isoforms are expressed differentially in beta and delta cells and, as a consequence, their responses to parasympathetic stimulation are different. Beta cells express the M3 isoform (whose agonists stimulate insulin secretion), whereas the M2 and M4 isoforms are involved in the parasympathetic inhibition of somatostatin secretion from delta cells [33]. In our studies, each of the three GPR120 agonists tested caused a marked inhibition of glucose-induced somatostatin secretion.…”

A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and β-arrestin 1

“…The crosstalk between these cells forms a finely tuned network that controls hormone release and maintains normal growth and survival of the islets. For example, somatostatin secreted from the islet delta cells regulates the responses of the islet beta and alpha cells to physiological changes [1,2]. An increase in the circulating glucose concentration triggers the release of somatostatin from the pancreatic delta cells, which exerts inhibitory effects on both insulin secretion from the beta cells and glucagon secretion from the alpha cells [1,3,4].…”

Endogenous Somatostatin Is Critical in Regulating the Acute Effects of l-Arginine on Growth Hormone and Insulin Release in Mice

“…Insulin, in turn, is thought to stimulate ␦-cells to release SST, which suppresses both insulin/glucagon release. However, recent data indicate that factors other than insulin may be involved in the glucose-induced rise in SST (28). Nevertheless, the critical role that SST plays in the paracrine regulation of islet function is supported by studies showing enhanced glucosestimulated insulin secretion (GSIS) in islets from SST-KO mice (13).…”