Somatostatin: mechanism of action in pancreatic islet beta-cells.
The widespread role of somatostatin (SRIF) as a mediator of function in the brain and gut has stimulated interest in it mechanism of action. We have examined the mode of action of SRIF in stimulus-secretion coupling in the pancreatic islet beta-cell to determine whether SRIF antagonizes the glucose-induced decrease in K+ permeability (PK). The influence of SRIF on 86Rb fluxes and insulin release in cultured rat islet cells, and also the electrical events recorded from cultured islets and microdissected mouse islets, was examined. In cultured islets, 100 ng/ml SRIF in the presence of 16.7 mM glucose inhibited the incidence of spike activity and evoked hyperpolarization. This effect was counteracted by 0.1 mM quinine and 20 mM tetraethylammonium (TEA), drugs that inhibit the Ca2+-sensitive or voltage-sensitive increase in PK, respectively. These agents also counteracted the inhibitory influence of SRIF on glucose-induced insulin release in cultured islets. SRIF disrupted the typical glucose-induced oscillatory pattern of electrical activity (burst activity) during continuous microelectrode recordings in mouse beta-cells, resulting in a transient 5mV hyperpolarization and a decrease in the frequency of generation of burst activity. The presence of 20 mm TEA prevented the influence of SRIF on the electrical activity. SRIF had no effect on the accumulation of 86Rb into islet cells obtained in the presence of 16.7 mM glucose. However, SRIF enhanced the rate of 86Rb efflux from cells exposed to glucose. SRIF-induced enhancement of 86Rb efflux was antagonized by TEA or quinine. These results indicate that SRIF may activate PK as its primary mode of action, an event that may be sufficient to reduce the accumulation of intracellular Ca2+ thereby disrupting glucose-induced stimulus-secretion coupling.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D046508:Culture Techniques; D004594:Electrophysiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011188:Potassium / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D007328:Insulin; D013757:Tetraethylammonium Compounds; D013004:Somatostatin; D011803:Quinine; D012413:Rubidium; D011188:Potassium; D002118:Calcium