ISSN:
1432-0428
Keywords:
Keywords Endothelin-1
;
islet of Langerhans
;
mouse
;
ion fluxes
;
glucose
;
insulin secretion.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 μmol/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 45Ca2 + -efflux from 45Ca2 + -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 45Ca2 + -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 Ca2 + -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. [Diabetologia (1996) 39: 1030–1035]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00400650
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