Rasmussen Rasmus S, Langberg Ludvig S, Østergaard Frederikke, Nielsen Sophie W, Vestergaard Mark B, Skov-Jeppesen Kirsa, Hartmann Bolette, Johannesen Helle Hjorth, Holst Jens J, Haddock Bryan, Larsson Henrik B W, Rosenkilde Mette M, Asmar Ali, Andersen Ulrik B, Gasbjerg Lærke S
Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
Diabetes. 2025 Aug 1;74(8):1355-1366. doi: 10.2337/db25-0149.
Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution. 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 g). 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 MRI, hepatic oxygen consumption by T2*, and plasma glucose, insulin, C-peptide, glucagon, GIP, GIPR-An, glucagon-like peptide 2, and bone metabolism markers 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 with 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.
Administration of the gut hormone glucose-dependent insulinotropic polypeptide (GIP) increases splanchnic blood flow. We investigated the role of endogenous GIP in splanchnic blood flow regulation using a receptor antagonist in humans. Oral glucose ingestion increased blood flow in the superior mesenteric artery by ∼70%, and the increase was significantly lower during concurrent infusion of the GIP receptor antagonist. Thus, endogenous GIP contributed ∼22% of the postprandial increase in superior mesenteric artery blood flow. We have identified a novel physiological aspect of vascular biology related to the GIP receptor in humans. Treatments targeting the GIP receptors are likely to affect splanchnic blood flow.
胃肠激素对于营养物质的处理和葡萄糖代谢的调节至关重要，并且可能影响餐后血液再分布。在一项针对10名健康男性的随机交叉设计研究中，在口服葡萄糖（75克）期间输注葡萄糖依赖性促胰岛素多肽（GIP）受体拮抗剂（GIPR - An）GIP(3 - 30)NH2，研究了GIP在内脏血流调节中的作用。在五个独立的实验环节中，我们分别研究了GIP(1 - 42)、有无口服葡萄糖时的GIPR - An、单独口服葡萄糖以及生理盐水输注对照。在所有实验环节中，通过相位对比磁共振成像评估血流，通过T2*评估肝脏氧消耗，并通过频繁采血检测血浆葡萄糖、胰岛素、C肽、胰高血糖素、GIP、GIPR - An、胰高血糖素样肽2以及骨代谢标志物。我们发现，在空腹状态下，GIP(1 - 42)可使肠系膜上动脉血流增加约10%。单独口服葡萄糖可使肠系膜上动脉平均血流较基线增加约70%，门静脉血流增加约40%。在口服葡萄糖同时输注GIPR - An期间，肠系膜上动脉血流降低约22%。激素输注对肝动脉和腹腔动脉血流无影响。与输注生理盐水相比，口服葡萄糖期间输注GIPR - An导致胰岛素分泌降低，羧基末端胶原交联物（骨吸收生物标志物）水平升高，而胰高血糖素水平不受GIP注射和GIPR - An输注的影响。我们得出结论，内源性GIP可增加内脏血流，并促成健康男性餐后肠道充血。
给予肠道激素葡萄糖依赖性促胰岛素多肽（GIP）可增加内脏血流。我们在人体中使用受体拮抗剂研究了内源性GIP在内脏血流调节中的作用。口服葡萄糖可使肠系膜上动脉血流增加约70%，在同时输注GIP受体拮抗剂期间，这一增加显著降低。因此，内源性GIP促成了餐后肠系膜上动脉血流增加的约22%。我们确定了人类中与GIP受体相关的血管生物学的一个新的生理方面。针对GIP受体的治疗可能会影响内脏血流。
