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.