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Enhanced Endosomal Signaling and Desensitization of GLP-1R vs GIPR in Pancreatic Beta Cells

Endocrinology. 2023-03; 
Yusman Manchanda, Stavroula Bitsi, Shiqian Chen, Johannes Broichhagen, Jorge Bernardino de la Serna, Ben Jones, Alejandra Tomas
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摘要

The incretin receptors, glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), are prime therapeutic targets for the treatment of type 2 diabetes (T2D) and obesity. They are expressed in pancreatic beta cells where they potentiate insulin release in response to food intake. Despite GIP being the main incretin in healthy individuals, GLP-1R has been favored as a therapeutic target due to blunted GIPR responses in T2D patients and conflicting effects of GIPR agonists and antagonists in improving glucose tolerance and preventing weight gain. There is, however, a recently renewed interest in GIPR biology, following the realization that GIPR responses can be resto... More

关键词

GIPR, GLP-1R, beta cell, incretin, signal compartmentalization, trafficking
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