Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats
Abstract
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.
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The animal findings that insulin acts in the brain to reduce food intake were repeatedly, although not unanimously, corroborated.
“These findings were repeatedly, 59,60 although not unanimously, 61 corroborated in animals.”
From Intranasal insulin (2021) · cites this paper as [61]
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- Authors
- Jessen, L., Clegg, D. J., & Bouman, S. D.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- University of Cincinnati (US)
- Corresponding author
- Bouman, Stephan D.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2010-01
- Volume
- 298
- Issue
- 1
- Pages
- R43-R50
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2087266477
- Cited by
- 29
- References
- 30
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2013: 3 · 2012: 3
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- insulin detemir, anorectic effect, dietary intake, body weight, melanotan II, hypothalamus, insulin analogues, rat strain differences, stereotactic injection
- MeSH terms
- Insulin Detemir, Animals, Anorexia, Body Weight, Disease Models, Animal, Dose-Response Relationship, Drug, Eating, Hypoglycemic Agents, Injections, Intraventricular, Insulin, Male, Time Factors, Rats, Sprague-Dawley, Rats, Long-Evans, Insulin, Long-Acting, Rats
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