Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats.
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.
Department of Insulin Pharmacology, Novo Nordisk, Maaloev, Denmark.
Lene
L
Jessen
Deborah J
DJ
Clegg
Stephan D
SD
Bouman
D000818:Animals; D000855:Anorexia / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir