Publication

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

Journal Paper/Review - Apr 1, 2002

Units
PubMed

Citation
Schultes B, Oltmanns K, Kern W, Born J, Fehm H, Peters A. The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 2002; 26:510-6.
Type
Journal Paper/Review (English)
Journal
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 2002; 26
Publication Date
Apr 1, 2002
Issn Print
0307-0565
Pages
510-6
Brief description/objective

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.