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Differential Sensitivity of Men and Women to Anorexigenic and Memory-Improving Effects of Intranasal Insulin

Department of Neuroendocrinology (C.B., J.B., M.H.) and Internal Medicine I (W.K.), University of Lübeck, 23538 Lübeck, Germany; and Interdisciplinary Obesity Center East-Switzerland (B.S.), Kantonsspital St. Gallen, CH-9400 Rorschach, Switzerland

Address all correspondence and requests for reprints to: Christian Benedict, Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Hs 23a, 23538 Lübeck, Germany. 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.

Objectives: Our objectives were 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: A total of 32 healthy, normal-weight subjects (14 men, 18 women) were intranasally administered 160 IU regular human insulin or vehicle before performing a hippocampus-dependent two-dimensional-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 is 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.

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