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This version published online on January 29, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2606
A more recent version of this article appeared on April 1, 2008
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Submitted on November 26, 2007
Accepted on January 22, 2008

Differential sensitivity of men and women to anorexigenic and memory improving effects of intranasal insulin

Christian Benedict*, Werner Kern, Bernd Schultes, Jan Born, and Manfred Hallschmid

Department of Neuroendocrinology, University of Lübeck, Germany; Internal Medicine I, University of Lübeck, Germany; Interdisciplinary Obesity Center East-Switzerland, Kantonsspital St. Gallen, Switzerland

* To whom correspondence should be addressed. E-mail: benedict{at}kfg.uni-luebeck.de.

Context: Brain insulin is critically involved in the regulation of body weight and memory processing. Long-term administration of intranasal insulin reduces body weight in men but not in women while improving hippocampus-dependent memory processing in both genders.

Objective: To assess the effects of a single dose of intranasal insulin on food intake and memory function in men and women and to determine any gender differences.

Methods: Thirty-two healthy, normal-weight subjects (14 men, 18 women) were intranasally administered 160 IU regular human insulin or vehicle before performing a hippocampus-dependent 2-D-object location task, a working memory task (digit span) and a hippocampus-independent mirror tracing task. Subsequently, food intake from an ad libitum breakfast buffet was measured.

Results: Insulin treatment decreased food intake in men but not in women (difference to placebo condition, men: -192.57 ± 78.48 kcal, P<0.03; women: 18.54 ± 42.89 kcal, P>0.67). In contrast, hippocampus-dependent memory and working memory were improved in women (P<0.03, P<0.05, respectively) whereas men did not benefit from acute insulin treatment (P>0.17, P>0.20). Performance on the hippocampus-independent mirror tracing task was not affected by insulin in women or men.

Conclusions: In accordance with animal data, results indicate that men are more sensitive than women to the acute anorexigenic effect of central nervous insulin signaling whereas insulin's beneficial effect on hippocampus-dependent memory functions are more pronounced in women. Our findings provide support for the notion of a fundamental gender difference in central nervous insulin signaling that pertains to the regulation of energy homeostasis and memory functions.


Key words: Insulin • Central nervous system • Food intake • Memory • Gender







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