title: 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 μg) with glucose (1 g/kg) led to decreased plasma insulin content (2.3±0.5 ng insulin/ml versus 4.5±0.5 ng/ml at t=5 min, P<0.001) and elevated blood glucose levels compared with those of the controls (29.19±1.3 mmol/l versus 23.5±1.7 mmol/l, P<0.05). In contrast, central i.c.v. injection of BIM23014C (0.75 μg) had no significant effect on either plasma insulin (3.3±0.4 ng/ml, P>0.05) or blood glucose levels (23.5±1.7 mmol/l, P>0.05) although i.v. administration of this dose increased blood glucose concentrations (32.3±0.7 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.
authors: Diabetes Research GroupDivision of Diabetes and Nutritional Sciences, King's College London, 2.27 Henrietta Raphael Building, Guy's Campus, London SE1 1UL, UK astrid.hauge_evans@kcl.ac.uk.
authors: Astrid C
authors: AC
authors: Hauge-Evans
authors: Diabetes Research GroupDivision of Diabetes and Nutritional Sciences, King's College London, 2.27 Henrietta Raphael Building, Guy's Campus, London SE1 1UL, UK.
authors: James
authors: J
authors: Bowe
authors: Diabetes Research GroupDivision of Diabetes and Nutritional Sciences, King's College London, 2.27 Henrietta Raphael Building, Guy's Campus, London SE1 1UL, UK.
authors: Zara J
authors: ZJ
authors: Franklin
authors: Diabetes Research GroupDivision of Diabetes and Nutritional Sciences, King's College London, 2.27 Henrietta Raphael Building, Guy's Campus, London SE1 1UL, UK.
authors: Zoheb
authors: Z
authors: Hassan
authors: Diabetes Research GroupDivision of Diabetes and Nutritional Sciences, King's College London, 2.27 Henrietta Raphael Building, Guy's Campus, London SE1 1UL, UK.
authors: Peter M
authors: PM
authors: Jones
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002490:Central Nervous System / Q000502:physiology*; D004333:Drug Administration Routes; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin
keywords: CNS; insulin secretion; intracerebroventricular; somatostatin