The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is secreted from enteroendocrine K cells in the small intestine following food intake. Exogenous GIP stimulates glucagon secretion during fasting at low blood sugar and exerts anabolic effects in fat and bone in healthy individuals. Using the GIP receptor antagonist GIP(3-30)NH2, we investigated the effects of endogenous GIP in humans during fasting.

In a randomized, placebo-controlled, double-blind, crossover study comprising two experimental days, 12 healthy participants (7 men, 5 women; mean (±SEM) age 35±4 years; mean BMI 38 ±1.6 kg/m2; mean body fat percentage 37 ± 2.2%) received 180-minute infusions of GIP(3-30)NH2 (1,000 pmol/kg/min) and placebo (saline), respectively, after 10 hours of fasting. An ad libitum meal was provided at time 180 min, during continuous infusion.

Comparing paired values for each participant, baseline-subtracted plasma glucose was higher during GIP(3-30)NH2infusion compared to placebo (mean bsAUC0-180 (±SEM) -53.6 ± 12.2 vs. -31.7 ± 6.6 min×mmol/L, P = 0.031) whereas systolic blood pressure (P = 0.44), diastolic blood pressure (P = 0.59), pulse rate (P = 0.92) and ad libitum food intake (P = 0.31) were unaffected.

In conclusion, endogenous GIP seem to have glucose-lowering effects in obese individuals in the fasting state.

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Disclosure

F. Koefoed-Hansen: None. H. Kizilkaya: None. M.M. Helsted: None. N.E. Sørum: None. B. Hartmann: Board Member; Bainan Biotech. F.K. Knop: Advisory Panel; AstraZeneca. Consultant; AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. Advisory Panel; Sanofi. Speaker's Bureau; Lundbeck. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics.

© 2024 by the American Diabetes Association
2024
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