Thyrotropin-releasing hormone and insulin release: in vitro studies with islets of normal and dysthyroid mice.
Pancreatic islets contain large-quantities of thyrotropin-releasing hormone (TRH) and of its metabolite Histidyl-Proline diketopiperazine (Cyclo His-Pro). The effects of these two putative neurotransmitters on the pancreatic B-cell function have been evaluated in vitro, with islets of normal or dysthyroid mice. TRH and Cyclo His-Pro (10(-11)-10(-6) M) were without effect on insulin release induced by 10-20 mM glucose in islets of normal mice. They transiently accelerated the slow waves of membrane potential triggered in B cells by 10 mM glucose, but did not cause any sustained change in overall electrical activity, and did not affect the rate of 86Rb+ efflux from islet cells. They were also ineffective when insulin release was stimulated by leucine or arginine, or was potentiated by forskolin, an activator of the adenylate cyclase. Hyperthyroidism (induced by injections of thyroxine) caused a fall in islet insulin content, but augmented the 2 phases of glucose-induced release. On the other hand, hypothyroidism (induced by a low iodine diet and propylthiouracil) caused an increase in islet insulin content, but depressed the second phase of release. TRH did not affect either phase of insulin release by islets of hyperthyroid or hypothyroid mice. These results show that pancreatic B cells are not a target for TRH and Cyclo His-Pro.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006980:Hyperthyroidism / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D007328:Insulin; D010456:Peptides, Cyclic; D010879:Piperazines; D005576:Colforsin; D013973:Thyrotropin-Releasing Hormone; D001120:Arginine; D007930:Leucine; D005947:Glucose; C015924:histidyl-proline diketopiperazine