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- W2013216962 abstract "Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα o proteins or from combined inactivation of Gα o , Gα i1 , Gα i2 , and Gα i3 isoforms. However, the specific role of Gα i2 in pancreatic β-cells still remains unknown. In global (Gα i2 −/− ) and β-cell-specific (Gα i2 βcko ) gene-targeted Gα i2 mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca 2+ measurements were used to characterize Gα i2 function in vitro. Gα i2 −/− and Gα i2 βcko mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα i2 −/− and Gα i2 βcko mice, whereas plasma glucose concentrations were unchanged in Gα i2 −/− but significantly increased in Gα i2 βcko mice. These findings indicate a novel albeit unexpected role for Gα i2 in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα i2 -deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by l-arginine or l-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα i2 . In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid l-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα i2 showing that amino acid-induced insulin-release depends on Gα i2 ." @default.
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- W2013216962 date "2014-11-01" @default.
- W2013216962 modified "2023-09-27" @default.
- W2013216962 title "Insulin secretion stimulated by <scp>l</scp>-arginine and its metabolite <scp>l</scp>-ornithine depends on Gα<sub>i2</sub>" @default.
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- W2013216962 doi "https://doi.org/10.1152/ajpendo.00337.2014" @default.
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