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Glucose-dependent Insulinotropic Polypeptide is Involved in Postprandial Regulation of Splanchnic Blood Supply

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posted on 2025-05-30, 17:28 authored by Rasmus S. Rasmussen, Ludvig S. Langberg, Frederikke Østergaard, Sophie W. Nielsen, Mark B. Vestergaard, Kirsa Skov-Jeppesen, Bolette Hartmann, Helle Hjorth Johannesen, Jens J. Holst, Bryan Haddock, Henrik B. W. Larsson, Mette M. Rosenkilde, Ali Asmar, Ulrik B. Andersen, Lærke S. Gasbjerg

Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution as well. In a randomized cross-over design in 10 healthy men, the involvement of glucose-dependent insulinotropic polypeptide (GIP) in splanchnic blood flow regulation was investigated using an infusion of GIP receptor antagonist (GIPR-An, GIP(3-30)NH2) during ingestion of oral glucose (75 grams). In five separate sessions, we investigated GIP(1-42), GIPR-An with and without oral glucose, oral glucose alone and a control saline infusion. Blood flow was assessed by phase-contrast magnetic resonance imaging, hepatic oxygen consumption by T2*, and plasma glucose, insulin, C-peptide, glucagon, GIP, GIPR-An, GLP-2, and bone metabolism markers were assessed by frequent blood sampling during all sessions. We found GIP(1-42) to stimulate blood flow in the superior mesenteric artery by ~10% in the fasting state. Oral glucose alone increased mean blood flow in the superior mesenteric artery by ~70% and portal vein by ~40% of baseline. During oral glucose ingestion with concurrent infusion of GIPR-An blood flow in the superior mesenteric artery was ~22% lower. The hormone infusions did not affect blood flow in the hepatic artery and the celiac artery. Infusion of GIPR-An during oral glucose ingestion resulted in lower insulin secretion and higher levels of carboxy-terminal collagen crosslinks (bone resorption biomarker) compared to saline infusion, whereas glucagon levels were unaffected by both the injection of GIP and the GIPR-An infusions. We conclude that endogenous GIP increases splanchnic blood flow and contributes to postprandial intestinal hyperemia in healthy men.

Funding

This work was supported by Rigshospitalet-Glostrup, Capital Region of Denmark, Department of Biomedical Sciences, University of Copenhagen, and by grants from Novo Nordisk Foundation (NNF18SA0034956), the European Foundation for the Study of Diabetes, Hørslev Foundation, King Christian the 10th Foundation, and A.P. Møller Foundation to LSG.

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