Search

Insulin acts in the brain to limit food intake and improve memory function. We have previously shown that 8 weeks of intranasal insulin delivered in four daily doses of 40 IU decrease body weight and enhance word list recall. In the present study, we investigated the effect on body composition, endocrine parameters, and memory performance of 8 weeks of once-daily administration of 160 IU in healthy men. We assumed that intranasal insulin administered before nocturnal sleep, a period of relative metabolic inactivity that moreover benefits memory formation, would be superior to insulin delivery in the morning and placebo administration. After a 2-week baseline period, healthy male normal-weight subjects (mean age, 27.1 +/- 0.9 years) received either placebo, 160 IU intranasal insulin in the morning, or 160 IU in the evening (n = 12 per group) for 8 consecutive weeks. Throughout the experiment, we measured body weight and body composition as well as circulating concentrations of glucose, insulin, adrenocorticotropin, cortisol, growth hormone, insulin-like growth-factor 1, adiponectin, and leptin. Declarative and procedural memory function was repeatedly assessed by means of, respectively, word list recall and word-stem priming. We found that neither morning nor evening insulin compared to placebo administration induced discernible changes in body weight and body composition. Delayed recall of words showed slight improvements by insulin administration in the evening, and serum cortisol concentrations were reduced after 2 weeks of insulin administration in the morning compared to the other groups. Results indicate that catabolic long-term effects of central nervous insulin delivery necessitate repetitive, presumably pre-meal delivery schedules. The observed memory improvements, although generally weaker than previously found effects, suggest that sleep after intranasal insulin administration may support its beneficial cognitive impact.

Study Objectives: In insulin-treated patients with diabetes, episodes of severe hypoglycemia often occur during sleep, which might reflect an altered counterregulation and reduced awareness. This study examined the influence of sleep on the counterregulatory response to hypoglycemia in healthy subjects. Design: Subjects participated in two experimental conditions; statistical tests relied on within subject comparisons. Setting: University hospital sleep laboratory. Participants: 15 healthy young men. Interventions: Hypoglycemia (2.8 mmol/l) was induced for 45 min by insulin infusion once during sleep and once at the same time of night while being awake. Measurements and Results: Counterregulatory hormone concentrations (epinephrine, norepinephrine, ACTH and cortisol) and sleep recordings were obtained. Differences in the hormonal responses to hypoglycemia between sleep and wake conditions remained non-significant, indicating that sleep does not exert a primary influence on the strength of counterregulation. However, the glycemic threshold for the onset of counterregulation was significantly changed during sleep: The average onset threshold for epinephrine and norepinephrine counterregulation was 3.3 ± 0.1 mmol/l for the wake condition and 2.7 t 0.1 mmol/l for the sleep condition (P < 0.001). A decrease in sleep depth coincided with the onset of the counterregulatory response, with most subjects showing signs of awakening. Conclusions: During sleep, the organism is less sensitive to hypoglycemia. Hypoglycemia per se has an awakening effect.