1. ¹Human Neurotransmitter Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia
2. ²Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
3. ³Endocrinology and Metabolism Division, Sepulveda Veterans Affairs Medical Center and David Geffin, the University of California-Los Angeles School of Medicine, Los Angeles, California.

Correspondence: Dr. Kazuko Masuo, Baker Heart Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia E-mail: kmasuo@baker.edu.au

Received 12 August 2004; Revised 15 September 2004; Accepted 15 September 2004.

Abstract

Background: 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.

Methods: 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/m²) and 38 overweight or obese (obese; BMI 25 kg/m²) 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.

Results: 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.

Conclusion: These results demonstrate that insulin sensitivity and adiposity affect the response of leptin and sympathetic nerve activity to acute postprandial hyperinsulinemia.