Differential effects of acute intranasal insulin administration on memory and food intake in men and women

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Background: Central nervous insulin is involved in the regulation of body weight and memory processing. Intracerebroventricular insulin administration decreases food intake in male but not in female rats while improving hippocampus-dependent memory in both males and females. We scrutinized acute effects of intranasal insulin on food intake and memory functions in men and women. Methods: Thirty-two healthy, normal-weight subjects (18 women) were intranasally administered 160 IU regular human insulin or vehicle according to a double-blind within-subject design 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 at an ad libitum breakfast buffet was registered. Results: Intranasal insulin decreased food intake in men but not in women (difference to placebo condition, men: -192.57±78.48kcal, p<0.03; women: 18.54±42.89kcal, p>0.67; Treat x Gender: p<0.02). In contrast, hippocampus-dependent memory and working memory were improved in female subjects (p<0.03, p<0.05, respectively) while men did not benefit from acute insulin treatment (p>0.17, p>0.20; Treat x Gender: p<0.01, p<0.03, respectively). Performance on the hippocampus-independent mirror tracing task was not affected by insulin either in women (p>0.50) or in men (p>0.86). 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 strong 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.