期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 6, 页码 3938-3951出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.385682
关键词
-
资金
- National Institutes of Health [U01DK089529, DK53012, DK22122, DK53761, HD26979, U42-RR-016600, U01 DK070430]
- NIDDK/Beckman Research Center (City of Hope) Integrated Islet Distribution Program [10028044]
- American Diabetes Association [7-11-BS-34]
- [DK19525]
Paracrine signaling between pancreatic islet beta-cells and alpha-cells has been proposed to play a role in regulating glucagon responses to elevated glucose and hypoglycemia. To examine this possibility in human islets, we used a metabolomic approach to trace the responses of amino acids and other potential neurotransmitters to stimulation with [U-C-13] glucose in both normal individuals and type 2 diabetics. Islets from type 2 diabetics uniformly showed decreased glucose stimulation of insulin secretion and respiratory rate but demonstrated two different patterns of glucagon responses to glucose: one group responded normally to suppression of glucagon by glucose, but the second group was non-responsive. The non-responsive group showed evidence of suppressed islet GABA levels and of GABA shunt activity. In further studies with normal human islets, we found that gamma-hydroxybutyrate (GHB), a potent inhibitory neurotransmitter, is generated in beta-cells by an extension of the GABA shunt during glucose stimulation and interacts with alpha-cell GHB receptors, thus mediating the suppressive effect of glucose on glucagon release. We also identified glycine, acting via alpha-cell glycine receptors, as the predominant amino acid stimulator of glucagon release. The results suggest that glycine and GHB provide a counterbalancing receptor-based mechanism for controlling alpha-cell secretory responses to metabolic fuels.
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