Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men

Abstract

Objective: Animal studies indicate a prominent role of brain insulin signaling in the regulation of peripheral energy metabolism. We determined the effect of intranasal insulin, which directly targets the brain, on glucose metabolism and energy expenditure in humans.

Research design and methods: In a double-blind, placebo-controlled, balanced within-subject comparison, 19 healthy normal-weight men (18-26 years old) were intranasally administered 160 IU human insulin after an overnight fast. Energy expenditure assessed via indirect calorimetry and blood concentrations of glucose, insulin, C-peptide, and free fatty acids (FFAs) were measured before and after insulin administration and the subsequent consumption of a high-calorie liquid meal of 900 kcal.

Results: Intranasal insulin, compared with placebo, increased postprandial energy expenditure, i.e., diet-induced thermogenesis, and decreased postprandial concentrations of circulating insulin and C-peptide, whereas postprandial plasma glucose concentrations did not differ from placebo values. Intranasal insulin also induced a transient decrease in prandial serum FFA levels.

Conclusions: Enhancing brain insulin signaling by means of intranasal insulin administration enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the control of whole-body energy homeostasis in humans.

FIG. 1.

Experimental schedule. Nineteen healthy subjects who had fasted overnight spent the experimental day sitting in bed in a supine position. Measurements of energy expenditure by 30-min periods of indirect calorimetry were performed during baseline (8:30–9:00 a.m.), immediately after intranasal insulin administration (9:45–10:15:00 a.m., 1.6 ml [160 IU] insulin and placebo, respectively; nose symbol), and five times following the standardized consumption of a predefined liquid meal of 900 kcal (cup symbol). Blood samplings for the determination of plasma glucose, serum insulin, C-peptide, and free fatty acids concentrations are indicated by syringe symbols.

FIG. 2.

Intranasal insulin enhances postprandial energy expenditure. Following baseline assessment of energy expenditure (EE) (expressed per kcal/min), acute effects of intranasal administration (nose symbol) of insulin (160 IU) (■), and placebo (□), respectively, on energy expenditure were frequently measured before and after ingestion of liquid food (900 kcal; cup symbol) for a total of 6.5 h (left panel). The rise in energy expenditure between baseline (8:30–9:45:00 a.m.) and the postprandial state (10:45:00 a.m.–3:15:00 p.m.) reflects the energy emitted mainly as heat during food metabolization (diet-induced thermogenesis [DIT]) (right panel). Data are means ± SEM; N = 19. *P < 0.05.

FIG. 3.

Intranasal insulin lowers postprandial serum insulin levels. Concentrations of plasma glucose (A), serum insulin (B), serum C-peptide (C), and serum free fatty acids (D) before and after acute intranasal administration (nose symbol) of intranasal insulin (160 IU; solid lines and black bars) and placebo (dashed lines and white bars) followed by the standardized ingestion of 900 kcal of liquid food (cup symbol). Postprandial levels (10:20 a.m.–4:00 p.m.) were also expressed as AUCs (right panels). All values are presented as means ± SEM. N = 19. *P < 0.05; **P < 0.01.