Insulin detemir is a novel human
insulin analog that does not show the usual propensity for
weight gain in diabetic patients. We speculated that this beneficial effect could be due to
insulin detemir exerting stronger
anorectic effects within the brain than other
insulins. To study the central effects of regular human
insulin and
insulin detemir on food intake, the present study was undertaken. We used acute intracerebroventricular
insulin injections to compare food intake and
body weight in rats fed ad libitum. Contrary to previously published data, we found that neither regular human
insulin (8 or 32 mU) nor
insulin detemir (1,290 pmol) reduced food intake in this model.
Melanotan-II was also injected intracerebroventricularly as a positive control, and significantly reduced food intake and
body weight, suggesting that our intracerebroventricular model is able to show
anorectic effects. A series of experiments was therefore conducted in which different set-ups were tested to investigate which factors would be required to produce the reported
anorectic effect of intracerebroventricular
insulin. Although we varied rat strain, stereotactic coordinates, formulations of
insulin and vehicle, dose, volume, and time of injection, the
anorectic effect of intracerebroventricular
insulin could not be replicated. Therefore, we suggest that acute intracerebroventricularly injected
insulin does not robustly inhibit food intake in rats. Based on our results, the acute intracerebroventricular injection procedure may not be a preferred method for studying the central
anorectic effects of
insulin in rats. Instead, administrations over time or locally in hypothalamic nuclei might be recommended.