Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men

Abstract

Results indicate that, in an acute setting, estrogen does not interact with central nervous insulin signaling in the control of eating behavior in healthy men. Insulin and estradiol rather exert independent inhibiting effects on macronutrient intake.

Intranasal insulin

“…35 Considering that other studies have failed to detect increases in CSF after IN insulin delivery (albeit of the insulin analogue lispro) to healthy volunteers, 36 further straightforward evidence for the central bioavailability of IN insulin (also in clinical cohorts such as patients with type 2 diabetes or AD) would be welcome evidence for the effectiveness of IN insulin delivery. The currently available devices for IN delivery range from simple nasal atomisers, 37 which have been proven to reliably trigger functional effects in healthy humans, [38][39][40][41][42][43][44][45][46][47] to more sophisticated appliances, which, for example, use a liquid hydrofluoroalkane propellant to eject a metered dose of insulin to target the upper third of the nasal cavity and thereby optimally reach the olfactory epithelium. 48 The lack of changes in primary outcome measures of the most recent multisite phase 2/3 trial on IN insulin in individuals with mild cognitive impairment (MCI) and AD that suffered from appliance-related hassles 49 (see below) demonstrates that there is still lots of room for methodological improvements in the domain of IN delivery.…”

“…Moreover, although studies in rodents suggest that systemic oestrogen may decrease the hypophagic effect of central insulin, 64 pretreating healthy young men with transdermal oestrogen for three consecutive days, which led to a 3.5-fold increase in their serum oestradiol concentrations, did not attenuate the suppression in calorie consumption triggered by IN insulin. 47 In experiments investigating the impact of 160 IU of IN insulin administered before nocturnal sleep, both men and women ate less from a standardised breakfast buffet when they had received IN insulin compared to placebo. 65 This effect, which was found in young and elderly participants alike, implies that an acute enhancement of the central nervous insulin signal in the evening exerts a surprisingly durable attenuating effect on food intake across sleep as a period of relative metabolic inactivity.…”

“…(For a summary of sex-specific effects of IN insulin, see Box 1; for a discussion of IN insulin effects on sleep-related parameters, see paragraph 4). However, the once-daily pre-sleep (or, for that matter, post-sleep) administration of 160 IU of IN insulin for 8 weeks did not reduce body weight in healthy men, 66 suggesting that delivery schedules synced to food intake 39,42,44,47 might be necessary for the catabolic impact of IN insulin to emerge.…”

“…63 Increasing circulating oestradiol at the same time as decreasing testosterone concentrations in healthy young men did not hamper the hypophagic effect of IN insulin. 47 (A comprehensive account of sex differences in the neuroendocrine control of food intake is provided elsewhere. 69 ) IN insulintriggered decreases in olfactory sensitivity were restricted to women in some, 70 but not all, 71 experiments that were performed in participants of both sexes.…”

Brain insulin sensitivity is linked to adiposity and body fat distribution

“…This function holds true in humans, where insulin affects important neuronal functions that underlie eating behavior 1 . Finally, insulin delivery to the human brain modulates food intake [3][4][5] .…”