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Am J Physiol Regul Integr Comp Physiol (October 28, 2009). doi:10.1152/ajpregu.90736.2008
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Submitted on August 29, 2008
Revised on October 13, 2009
Accepted on October 25, 2009

Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats

Lene Jessen1, Deborah J. Clegg2, and Stephan D Bouman1*

1 Novo Nordisk
2 UT Southwestern Medical Center

* To whom correspondence should be addressed. E-mail: sdbo{at}novonordisk.com.

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 (i.c.v.) 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 mU or 32 mU) nor insulin detemir (1290 pmol) reduced food intake in this model. Melanotan-II (MT-II) was also injected i.c.v. as a positive control, and significantly reduced food intake and body weight, suggesting that our i.c.v. 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 i.c.v. insulin. Although we varied rat strain, stereotactic coordinates, formulations of insulin and vehicle, dose, volume, and time of injection, the anorectic effect of i.c.v. insulin could not be replicated. Therefore we suggest that acute i.c.v. injected insulin does not robustly inhibit food intake in rats. Based on our results, the acute i.c.v. injection procedure may not be a preferred method for studying the central anorectic effects of insulin in rats. Instead, administrations over time or locally into hypothalamic nuclei might be recommended.







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