👤 Camilla Ditlev Lindhardt Johannesen

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. Show less

For decades, studies have tried to identify the cholesterol marker that best reflects risk of atherosclerotic cardiovascular disease(ASCVD). Comparing low-density-lipoprotein(LDL) cholesterol, non-high-density-lipoprotein(non-HDL) cholesterol, and apolipoprotein B(apoB) as ASCVD risk markers has been challenged by high correlation between them. Thus, discordance analyses, directly addressing disagreements between the cholesterol markers, have emerged. Approaches adopted to define discordance originate in one of three methods: discordance by cut-points, discordance by percentiles, or discordance by residuals. Commonly, concordant lipid levels serve as reference examining the association between discordant lipid levels with risk of ASCVD. Importantly, concordant reference groups present heterogeneity of clinical relevance across different discordance methods as concordant low lipid levels associate with lowest ASCVD risk while concordant high lipid levels associate with highest risk. Thus, results from different discordance approaches cannot be directly compared. Moreover, discordance between cholesterol markers is more frequently seen in individuals treated with lipid-lowering medication than in individuals not treated with lipid-lowering medication. Accordingly, studies performing discordance analyses have reported inconsistent and even conflicting results. Discordance by cut-points appears the most intuitive and clinically applicable method; results from these analyses suggest that elevated LDL cholesterol, non-HDL cholesterol, or apoB levels in individuals not treated with lipid-lowering medication confer increased ASCVD risk while in individuals treated with lipid-lowering medication, elevated non-HDL cholesterol and apoB levels best indicate residual risk. Results from discordance analyses comparing LDL cholesterol, non-HDL cholesterol, and apoB in risk of ASCVD as well as complexities of discordance analyses and considerations regarding interpretations are discussed in this review. Show less