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

International Journal of Obesity volume 26, pages 510–516 (2002)Cite this article

Abstract

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.

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Acknowledgements

We thank Christiane Zinke for her expert and invaluable laboratory assistance and Anja Otterbein for her organisational work.

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  1. Departments of Internal Medicine I and Clinical Neuroendocrinology, University of Luebeck, Luebeck, Germany

    B Fruehwald-Schultes, KM Oltmanns, W Kern, J Born, HL Fehm & A Peters

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  1. B Fruehwald-Schultes
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  3. W Kern
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Correspondence to B Fruehwald-Schultes.

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Fruehwald-Schultes, B., Oltmanns, K., Kern, W. et al. The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia. Int J Obes 26, 510–516 (2002). https://doi.org/10.1038/sj.ijo.0801942

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