GIP Acutely Blunts Insulin- and GLP-1-Induced Muscle Microvascular Perfusion.

Liu, Jia; Chun, Changzoon; Sin, Thomas K; Zhao, Fang; Aylor, Kevin W; Tushi, Nusrat J; Sun, Shengyi; Liu, Zhenqi · Diabetes · 2026

basic_science · Level V

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Abstract

Skeletal muscle microvasculature is essential for nutrient delivery and metabolic regulation, but the vascular actions of glucose-dependent insulinotropic polypeptide (GIP) in muscle are unknown. We investigated whether GIP regulates skeletal muscle microvascular perfusion and interacts with insulin and GLP-1 signaling. GIP receptors are expressed in vascular endothelium, yet GIP alone does not increase muscle perfusion and instead antagonizes insulin- and GLP-1-mediated microvascular recruitment via possibly angiotensin II type 1 receptor-dependent endothelin-1/nitric oxide imbalance. GIP acts as a conditional regulator of skeletal muscle microvascular perfusion, revealing a novel mechanism of tissue-specific incretin regulation of nutrient partitioning.