Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice

Søren Gregersen, J L Thomsen, Birgitte Brock, Kjeld Hermansen

43 Citationer (Scopus)

Abstract

Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l-1 mumol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p < 0.05). The effect of ET-1 is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p < 0.001), but not in the absence, of extracellular Ca2+. The rate of 45Ca(2+)-efflux from 45Ca(2+)-prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7 mmol/l glucose in the presence of extracellular Ca2+ (p < 0.001). A short-lived increase in 45Ca(2+)-efflux was also observed in the absence of extracellular Ca2+ (p < 0.05). It is suggested that the effects of ET-1 on insulin secretion are critically dependent on influx via Ca(2+)-channels. In addition, ET-1 transiently enhanced 86Rb(+)-efflux from 86Rb(+)-prelabelled islets both in the presence (p < 0.001) and in the absence (p < 0.001) of extracellular Ca2+ suggesting that ET-1 does not elicit insulin secretion by inhibition of the potassium permeability. Our study provides evidence that ET-1 stimulates insulin secretion via a direct effect on the islets of Langerhans.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind39
Udgave nummer9
Sider (fra-til)1030-5
Antal sider6
ISSN0012-186X
StatusUdgivet - sep. 1996
Udgivet eksterntJa

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