Pancreatic α Cell-Derived Glucagon-Related Peptides Are Required for β Cell Adaptation and Glucose Homeostasis

Cell Reports

Fabrizio Thorel¹  Pedro L. Herrera¹  Marc Stawiski²  Marianne Böni-Schnetzler²  Norina Koch²  Erez Dror²  Nicole Goetz²  Daniel T. Meier²  Elise Dalmas²  Shuyang Traub²  Friederike Schulze²  Marc Y. Donath²  Thierry M. Nordmann²  Valmir Makshana² 

[1] Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;Endocrinology, Diabetes, and Metabolism, University Hospital Basel, 4031 Basel, Switzerland;

关键词: GLP-1;    DPP-4;    glucagon;    insulin;    α cell;    β cell;    islet;    diabetes;    paracrine;    glucose homeostasis;    sitagliptin;   

DOI  :  10.1016/j.celrep.2017.03.005

来源: DOAJ

【 摘 要 】

Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α cell ablation and with α cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of α cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired. This was partly rescued with the DPP-4 inhibitor sitagliptin, but not with glucagon administration. In isolated islets from these mice, glucose-stimulated insulin secretion was heavily impaired and exogenous GLP-1 or glucagon rescued insulin secretion. These data highlight the importance of α cell-derived GLP-1 for glucose homeostasis during metabolic stress and may impact on the clinical use of systemic GLP-1 agonists versus stabilizing local α cell-derived GLP-1 by DPP-4 inhibitors in type 2 diabetes.

【 授权许可】

Unknown