GIP(3-30)NH2 antagonist reduces postprandial splanchnic blood flow in type 2 diabetes

In healthy individuals, endogenous glucose-dependent insulinotropic polypeptide (GIP) significantly increases postprandial blood flow in the arteria mesenterica superior, a key component of splanchnic circulation. However, in individuals with type 2 diabetes (T2D), the vascular biology linked to GIP receptor activation is often markedly impaired or even absent, leading to a perception that GIP's role in T2D is primarily insulinotropic and often diminished. This study aimed to clarify the contribution of endogenous GIP to postprandial splanchnic blood flow regulation in T2D, addressing a critical gap in understanding GIP's broader physiological impact beyond glucose metabolism in this population.

This randomized, single-blinded, placebo-controlled, crossover study involved 10 participants with type 2 diabetes (HbA1c >48 mmol/mol and <75 mmol/mol). Each participant underwent four separate interventions: oral glucose (75 g) + i.v. GIP(3-30)NH2; oral glucose (75 g) + i.v. saline; oral water + i.v. GIP(3-30)NH2; and oral water + i.v. saline. Participants were unaware of allocation, while investigators were aware. Splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus, and vena portae during oral glucose or water ingestion. Blood samples were collected for insulin, C-peptide, GIP, glucagon, and glucose analysis.