期刊
JCI INSIGHT
卷 4, 期 5, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.126742
关键词
-
资金
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) [F32 DK116542]
- American Diabetes Association [1-16-IBS-212, 1-18-JDF-017]
- NIH/NIDDK [R01 DK113103, R01 DK101991]
- NIH/National Institute on Aging [R21 AG050135]
- New Investigator Award from the Wisconsin Partnership Program
- Early Career Development Award from the Central Society for Clinical and Translational Research
- Molecular Biophysics Training Grant [T32GM08293]
- Wisconsin Alumni Research Foundation Dissertation Fellowship
- Canadian Institutes of Health Research [MOP310536]
Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for alpha to beta cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and nonmetabolic stimulation of mouse and human islets. This effect is due to reduced beta cell cAMP and affects the quantity but not dynamics of insulin release, indicating that PGDPs dictate the magnitude of insulin output in an isolated islet. In healthy mice, additional factors that stimulate cAMP can compensate for loss of PGDP signaling; however, input from alpha cells is essential to maintain glucose tolerance during the metabolic stress induced by high-fat feeding. These findings demonstrate an essential role for alpha cell regulation of beta cells, raising the possibility that abnormal paracrine signaling contributes to impaired insulin secretion in diabetes. Moreover, these findings support reconsideration of the role for alpha cells in postprandial glucose control.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据