Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans

Circulating plasma insulin and glucose levels are thought to be major regul ators of leptin secretion. There is evidence from in vitro and animal exper iments that glucose metabolism rather than insulin alone is a main determin ant of leptin expression. Here, we tested the hypothesis that in humans als o leptin secretion is primarily regulated by glucose uptake and only second arily by plasma insulin and glucose. In 30 lean and healthy men we induced 4 experimental conditions by using the blood glucose clamp technique. A tot al of 60 hypoglycemic and euglycemic clamps, lasting 6 h each, were perform ed. During these clamps insulin was infused at either high (15.0 mU/min.kg) or low (1.5 mU/min.kg) rates, resulting in low-insulin-hypo, high-insulin- hypo, low-insulin-eu, and high-insulin-eu conditions. Serum leptin increase d from 0-360 min by 20.5 +/- 4.1% in the low-insulin-hypo, 33.6 +/- 7.6% in the high-insulin-hypo, 39.6 +/- 6.0% in the low-insulin; eu, and 60.4 +/- 7.6% in the high-insulin-eu condition. Multiple regression analysis reveale d a significant effect of circulating insulin (low us. high insulin; P = 0. 001) and blood glucose (hypoglycemia us. euglycemia; P = 0.001) on the rise of serum leptin. However, when the total amount of dextrose infused during the clamp (grams of dextrose per kg BW) was included into the regression m odel, this variable was significantly related to the changes in serum lepti n (P = 0.001), whereas circulating insulin and glucose had no additional ef fect. These findings in humans support previous in vitro data that leptin s ecretion is mainly related to glucose metabolism.