Systemic insulin is considered to serve as a major negative feedback signal in the central nervous regulation of food intake. Accordingly, euglycemic infusion of regular human insulin (RI) has been shown to reduce hunger in a dose dependent fashion. Due to its increased lipophility, the long-acting insulin analogue insulin detemir (DI) might cross the bloodbrain barrier faster and in higher quantities than RI and exceed stronger anorexigenic effects. To test this hypothesis, we measured food intake after DI and RI administration. 15 healthy, normal-weight men were examined in two hyperinsulinemic euglycemic clamp experiments taking place in the morning after an overnight fast. In both conditions, an insulin bolus injection (DI, 90 mU/kg body weight; RI, 17.75 mU/kg) was followed by a steady 90 min insulin infusion (2.0 vs 1.0 mU/kg per min). To compensate for the relatively slower onset of the action of DI, a higher dosage was chosen to induce comparable peripheral effects of both compounds. Mean blood glucose levels during the clamp period were likewise comparable between conditions (P<0.384). Twenty minutes after infusion, subjects were allowed to eat ad libitum from a standardized breakfast buffet. ID reduced total food intake in comparison to RI (1257±82 vs 1560±139 kcal, P<0.04). This effect was also observed for the intake of protein (P=0.004), tended to be observed for the intake of carbohydrates (P=0.063) but not of fat (P=0.201). Although systemic contributions to the observed effects cannot be ruled out, our data suggest that compared to regular human insulin, insulin detemir induces stronger effects on brain networks that control food intake. They further support the notion of insulin as an anorexigenic feedback signal in the central nervous regulation of energy homeostasis.
03 - 07 May 2008
European Society of Endocrinology