Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo.
The demonstration of leptin receptors on the pancreatic beta-cells suggests the possibility of direct actions of leptin on insulin secretion. In vitro studies on islets or perfused pancreas and beta-cell lines produced inconsistent results. We performed an in vivo study to distinctly examine whether leptin has an effect on glucose-stimulated insulin secretion. Young chronically catheterized Sprague-Dawley rats (n = 28) were subjected to a 4-h hyperglycemic clamp study (approximately 11 mmol/l). At minute 120 to 240, rats were assigned to receive either saline or leptin (0.1, 0.5, and 5 microg x kg(-1) x min) infusion. Leptin decreased plasma insulin levels abruptly, and an approximately twofold decrease in plasma insulin levels compared with saline control was sustained over the 2 h of the study (14.8 +/- 5.8 vs. 34.8 +/- 2.6 ng/ml with leptin and saline infusion, respectively, P < 0.001). Moreover, a dose-dependent decrease in plasma insulin levels was noted (r = -0.731, P < 0.01). Since milrinone, an inhibitor of cAMP phosphodiesterase (PDE) 3, did not reverse the effect of leptin on glucose-induced insulin secretion, its action may be independent of PDE3. These findings suggest that acute physiological increase in plasma leptin levels acutely and significantly inhibits glucose-stimulated insulin secretion in vivo. The site of leptin effects on insulin secretion remains to be determined.
Cases
J A
JA
Diabetes Research and Training Center and the Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Gabriely
I
I
Ma
X H
XH
Yang
X M
XM
Michaeli
T
T
Fleischer
N
N
Rossetti
L
L
Barzilai
N
N
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood*; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D020738:Leptin; D010726:Phosphodiesterase Inhibitors; D020105:Milrinone