effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia

• Published in: International Journal of Obesity Vol. 26; no. 4; pp. 510 - 516
• Main Authors: Fruehwald-Schultes, B, Oltmanns, K.M, Kern, W, Born, J, Fehm, H.L, Peters, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.2002; Nature Publishing
• Subjects: Adult; Analysis. Health state; Biological and medical sciences; Blood Glucose - analysis; blood serum; Body Mass Index; Body weight; Epidemiology; Functional investigation of endocrine glands and genital system; General aspects; Glucose; Glucose Clamp Technique; Humans; Hydrocortisone - blood; hyperinsulinemia; Hyperinsulinism - blood; Hypoglycemia; insulin; Insulin Resistance; Internal medicine; Investigative techniques, diagnostic techniques (general aspects); Kinetics; leptin; Leptin - blood; Male; Medical research; Medical sciences; men; Plasma; Public health. Hygiene; Public health. Hygiene-occupational medicine; secretion; Germany; Hyperinsulinemia; Seeds; Induction; Secretion; Concentration; Glucose; Insulin; Uptake; Resistance; Body mass index; Regulation(control); Sensitivity resistance; Leptin; Serum
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0801942

OBJECTIVE: Insulin is thought to be an important regulator of leptin secretion. However, increasing evidence suggests that insulin-mediated glucose uptake rather than insulin per se regulates circulating leptin concentration. Here, we hypothesised that a reduction of insulin sensitivity, ie insulin resistance, will diminish the stimulatory effect of insulin on leptin secretion as a consequence of decreased insulin-mediated glucose uptake. DESIGN: Changes in serum leptin concentration during 30 hyperinsulinaemic-hypoglycaemic clamps were studied after induction of different levels of insulin resistance in normal-weight men. In 15 subjects insulin sensitivity was reduced by exposing them to a 2.5 h antecedent hypoglycaemia (3.1 mmol/l) induced by a high rate of insulin infusion (15.0 mU/min/kg) on the day before the proper experiment ('ante-hypo' condition). In the other 15 subjects no antecedent hypoglycaemia was induced ('control' condition). The proper experiment on both conditions was a 6 h stepwise hypoglycaemic clamp induced by a constant rate of insulin infusion (1.5 mU/min/kg). SUBJECTS: Experiments were carried out in 30 lean healthy subjects (age, mean±s.e.m., 26±1 y; body mass index, 23.1±0.6 kg/m2). RESULTS: As expected, glucose demand during the clamp was lower in the ante-hypo condition than in the control condition (gram of glucose infused per kilogram body weight, 1.52±0.16 vs 2.01±0.17 g/kg; P<0.05). During the clamp, leptin levels increased by 25.4±4.3% in the control condition (P<0.05), but not in the ante-hypo condition (+4.8±4.5%; P>0.25). Thus, serum leptin response to the clamp significantly differed between the two conditions (P<0.01). Across both conditions, the increase of leptin levels during the clamp was correlated with the amount of glucose infused (r=0.37; P<0.05). CONCLUSION: Considering that insulin concentrations were identical during both clamp conditions, the data indicate that experimentally-induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion.