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

B. Fruehwald-Schultes*, K. M. Oltmanns, W. Kern, J. Born, H. L. Fehm, A. Peters

*Corresponding author for this work
18 Citations (Scopus)


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±0.1 6 vs 2.01±0.1 7 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.

Original languageEnglish
JournalInternational Journal of Obesity
Issue number4
Pages (from-to)510-516
Number of pages7
Publication statusPublished - 2002

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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