Differential Sensitivity of Men and Women to Anorexigenic and Memory-Improving Effects of Intranasal Insulin

Abstract

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.

Central nervous insulin administration before nocturnal sleep decreases breakfast intake in healthy young and elderly subjects

“…We have previously shown that intranasal insulin administered to young male subjects in the fasted state (Benedict et al, 2008) acutely decreases food intake, and reduces the intake of palatable snacks in young female subjects after lunch . The latter effect concerned post-prandial snacking in the afternoon and likely resulted from effects on reward-processing pathways, which may be assumed to have also played a role in the present experiments, although our study design clearly does not allow for a differentiation between reward-and hunger-related aspects of eating.…”

“…They were told to abstain from caffeine and to follow their usual dinner routines around 1800-1900 h. Participants arrived at the sleep lab at 2000 h. Adherence to the instructions for the experimental day was confirmed and an intravenous catheter was placed in a vein of the dominant arm. At 2120 h, participants underwent a memory test battery (see Feld et al, 2016, for details and respective results in the group of young subjects) before receiving intranasal insulin or placebo via sixteen 0.1-ml puffs (8 per nostril) in 1-min intervals, amounting to a total dose of 1.6 ml insulin (160 IU) or placebo at 2220 h. This dose was chosen in order to enable comparisons with previous studies on the role of central nervous insulin in the acute regulation of food intake (Benedict et al, 2008;Hallschmid et al, 2012). Subjects went to bed at 2300 h for 8 h of polysomnographically recorded sleep, resulting in an overnight fast of at least 12 h in all subjects.…”

“…Both leptin and insulin circulate in direct proportion to the size of body fat stores and reach the CNS via active, saturable transport mechanisms across the blood-brain barrier (Baura et al, 1993;Schwartz et al, 1996;William and Banks, 2001). Studies in animals (Woods et al, 1979;McGowan et al, 1992;Air et al, 2002) and humans (Benedict et al, 2008;Hallschmid et al, 2012) have conclusively shown that insulin administered directly to the brain reduces food intake, independent of its peripheral glucoregulatory action. In humans, the inhibitory effect of central nervous insulin on food intake has been mainly investigated by means of the intranasal route of peptide administration (Hallschmid et al, 2004aBenedict et al, 2008), a non-invasive method of substance delivery to the brain that largely bypasses the blood-brain barrier (Born et al, 2002;Dhuria et al, 2010).…”

“…Studies in animals (Woods et al, 1979;McGowan et al, 1992;Air et al, 2002) and humans (Benedict et al, 2008;Hallschmid et al, 2012) have conclusively shown that insulin administered directly to the brain reduces food intake, independent of its peripheral glucoregulatory action. In humans, the inhibitory effect of central nervous insulin on food intake has been mainly investigated by means of the intranasal route of peptide administration (Hallschmid et al, 2004aBenedict et al, 2008), a non-invasive method of substance delivery to the brain that largely bypasses the blood-brain barrier (Born et al, 2002;Dhuria et al, 2010). Intranasal administration of 160 IU insulin to healthy, fasted young subjects reduced calorie intake in male, but not female participants (Benedict et al, 2008).…”

“…In humans, the inhibitory effect of central nervous insulin on food intake has been mainly investigated by means of the intranasal route of peptide administration (Hallschmid et al, 2004aBenedict et al, 2008), a non-invasive method of substance delivery to the brain that largely bypasses the blood-brain barrier (Born et al, 2002;Dhuria et al, 2010). Intranasal administration of 160 IU insulin to healthy, fasted young subjects reduced calorie intake in male, but not female participants (Benedict et al, 2008). Accordingly, intranasal insulin treatment (4 × 40 IU/day) for 8 weeks resulted in loss of body weight and body fat in men but not in women (Hallschmid et al, 2004a).…”