详细记录  
题名:Regulation of glucagon secretion in normal and diabetic human islets by gamma-hydroxybutyrate and glycine.
作者:LI C; LIU C; NISSIM I; CHEN J; CHEN P; DOLIBA N; ZHANG T; NISSIM I; DAIKHIN Y; STOKES D; YUDKOFF M; BENNETT MJ; STANLEY CA; MATSCHINSKY FM; NAJI A;
来源:J Biol Chem. 2013 Feb 8;288(6):3938-51. doi: 10.1074/jbc.M112.385682. Epub 2012 [ IF= 0.00 ] ]
URL :10.1074/jbc.M112.385682
日期:20130228
摘要: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-(13)C]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.

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