Acute hyperinsulinemia reduces plasma leptin levels in insulin-sensitive Japanese men

Abstract

Elevated plasma leptin levels have been demonstrated in obesity and hypertension. These conditions are documented as insulin-resistant states with sympathetic overactivity. However, the relation between plasma insulin, leptin levels, and sympathetic nerve activity, especially after meals, has not been established. To evaluate the impact of insulin sensitivity and obesity on the response of plasma leptin to acute physiologic insulin elevation, we studied 31 nonobese (body mass index [BMI] < 25 kg/m(2)) and 38 overweight or obese (obese; BMI >/= 25 kg/m(2)) normotensive men. Using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the subjects were subdivided into insulin-sensitive (HOMA-IR <2.5) and insulin-resistant (HOMA-IR >/=2.5) groups. There were 11 nonobese and 28 obese men who were insulin-resistant. Blood pressure (BP), plasma glucose, insulin, leptin, and norepinephrine (NE) levels were measured before and after 75-g oral glucose loading every 30 min for 120 min. In nonobese subjects, fasting plasma insulin and leptin levels and areas-under-the-curves (AUC) for insulin and leptin were significantly lower in the insulin-sensitive group than in the insulin-resistant group. In the insulin-sensitive group regardless of BMI, plasma leptin levels decreased after glucose loading. Plasma glucose, insulin, NE, and BP levels increased in nonobese insulin-sensitive subjects after glucose loading, whereas in obese insulin-sensitive subjects, plasma NE and BP did not change in response to glucose. In insulin-resistant subjects regardless of BMI, marked elevations in plasma insulin did not cause any change in plasma leptin, NE, and BP levels. These results demonstrate that insulin sensitivity and adiposity affect the response of leptin and sympathetic nerve activity to acute postprandial hyperinsulinemia.