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

J Clin Endocrinol Metab. 2008 Apr;93(4):1339-44. doi: 10.1210/jc.2007-2606. Epub 2008 Jan 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adult
  • Blood Glucose / analysis
  • Eating / drug effects*
  • Female
  • Hippocampus / physiology
  • Humans
  • Insulin / administration & dosage*
  • Male
  • Memory / drug effects*
  • Sex Characteristics
  • Signal Transduction


  • Blood Glucose
  • Insulin