Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS

Abstract

The inhibitory effect of somatostatin (SST) on insulin secretion in vivo is attributed to a direct effect on pancreatic beta cells, but this is inconsistent with some in vitro results in which exogenous SST is ineffective in inhibiting secretion from isolated islets. We therefore investigated whether insulin secretion from the pancreatic islets may partly be regulated by an indirect effect of SST mediated via the CNS. Islet hormone secretion was assessed in vitro by perifusion and static incubations of isolated islets and in vivo by i.v. or i.c.v. administration of the SST analogue BIM23014C with an i.v. glucose challenge to conscious, chronically catheterised rats. Hormone content of samples was assessed by ELISA or RIA and blood glucose levels using a glucose meter. Exogenous SST14/SST28 or BIM23014C did not inhibit the release of insulin from isolated rodent islets in vitro, whereas peripheral i.v. administration of BIM23014C (7.5 mg) with glucose (1 g/kg) led to decreased plasma insulin content (2.3G0.5 ng insulin/ml versus 4.5G0.5 ng/ml at tZ5 min, P!0.001) and elevated blood glucose levels compared with those of the controls (29.19G1.3 mmol/l versus 23.5G1.7 mmol/l, P!0.05). In contrast, central i.c.v. injection of BIM23014C (0.75 mg) had no significant effect on either plasma insulin (3.3G0.4 ng/ml, PO0.05) or blood glucose levels (23.5G1.7 mmol/l, PO0.05) although i.v. administration of this dose increased blood glucose concentrations (32.3G0.7 mmol/l, P!0.01). BIM23014C did not measurably alter plasma glucagon, SST, GLP1 or catecholamine levels whether injected i.v. or i.c.v. These results indicate that SST does not suppress insulin secretion by a centrally mediated effect but acts peripherally on islet cells.

Structural basis for delta cell paracrine regulation in pancreatic islets

“…Somatostatin is a powerful paracrine inhibitor of islet alpha and beta cells, which express different isoforms of the somatostatin receptor 10,11 . These receptors enable somatostatin-dependent suppression of glucagon and insulin release 12 , indirectly impacting glucose homeostasis 13,14 . Delta cells release somatostatin in response to acetylcholine 15 , glutamate 6 , urocortin3 (Ucn3) 16 , ghrelin 11 , and high glucose 17 .…”

Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors

“…Earlier work in rat islets showed that DA inhibits SST secretion via its actions on D 2 -like receptors 92 . This raises the possibility that the DA synthesized by αand β-cells also locally activates δ-cell D2R to inhibit SST secretion and thus removes SSTmediated inhibition of insulin and glucagon release 32,91,[93][94][95][96][97][98] . Such paracrine DA signaling that involves α-, β-, and δ-cells may offer an additional dimension to our understanding of the intra-islet regulation of hormone secretion.…”

Sex differences in body composition, metabolism‐related hormones, and energy homeostasis during aging in Wistar rats

“…n for each group is inside or at the top of the column level of estrogen, since estradiol deficiency, as seen in aged females, is known to decrease insulin sensitivity in the liver, skeletal muscle, and white adipose tissue; reduce GLUT4 expression in skeletal muscle and white adipose tissue; and stimulate food intake and gluconeogenesis (Foryst-Ludwig & Kintscher, 2010;Lu et al, 1998). The 18-month-old females in ad libitum conditions exhibited low plasma glucose, insulin, and triglyceride concentrations, indicating a possible decrease in intestinal absorption of glucose and triglycerides (Hahn et al, 1978;Hauge-Evans et al, 2015;Krejs et al, 1980;Wahren & Feling, 1976). The increased PRL concentration observed in older females may be due to the lack of response of hypothalamic tuberoinfundibular dopaminergic neurons or to a possible alteration of PRL receptors (Reymond, 1990).…”

“…Moreover, in the feeding animals, the highest glycemia in 3‐month‐old females could be a consequence of their low level of estrogen, since estradiol deficiency, as seen in aged females, is known to decrease insulin sensitivity in the liver, skeletal muscle, and white adipose tissue; reduce GLUT4 expression in skeletal muscle and white adipose tissue; and stimulate food intake and gluconeogenesis (Foryst‐Ludwig & Kintscher, 2010; Lu et al., 1998). The 18‐month‐old females in ad libitum conditions exhibited low plasma glucose, insulin, and triglyceride concentrations, indicating a possible decrease in intestinal absorption of glucose and triglycerides (Hahn et al., 1978; Hauge‐Evans et al., 2015; Krejs et al., 1980; Wahren & Feling, 1976).…”