Inhibition of glucose-induced insulin secretion by long-term preexposure of pancreatic islets to leptin.
Here we evaluated the effect of leptin on glucose-induced insulin secretion by normal rat pancreatic islets. We show in perifusion experiments that leptin had no acute effect on the secretory activity of beta-cells. However, following preexposure to leptin a pronounced time- and dose-dependent inhibition of both first and second phases of secretion was observed. Maximum inhibition was obtained at 24 h and with 100 nM leptin. This inhibition did not involve a decrease in cellular insulin content. It was also not observed with islets from fa/fa rats. Leptin thus inhibits insulin secretion by a mechanism which requires long-term preexposure to the hormone and which may involve alteration in beta-cell gene expression.
Roduit
R
R
Institute of Pharmacology and Toxicology, University of Lausanne, Switzerland.
Thorens
B
B
D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin; D008297:Male; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D007328:Insulin; D020738:Leptin; D011506:Proteins; D011994:Recombinant Proteins; D005947:Glucose