Endocrine Abstracts (2008) 16 OC1.8

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

Christian Benedict1, Werner Kern3, Bernd Schultes2, Jan Born1, Hendrik Lehnert3 & Manfred Hallschmid1

1Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany; 2Interdisciplinary Obesity Center East-Switzerland, Kantonsspital St Gallen, St Gallen, Switzerland; 3Internal Medicine I, University of Lübeck, Lübeck, Germany.

Background: Central nervous 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. Here, acute effects of intranasal insulin on food intake and memory functions were studied in men and women.

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.

Findings: 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 both sexes.

Interpretation: In accordance with animal data, our 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 first 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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