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The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice
Antonia Sassmann, … , Stefan Offermanns, Nina Wettschureck
Antonia Sassmann, … , Stefan Offermanns, Nina Wettschureck
Published May 3, 2010
Citation Information: J Clin Invest. 2010;120(6):2184-2193. https://doi.org/10.1172/JCI41541.
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Research Article Metabolism

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

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Abstract

A variety of neurotransmitters, gastrointestinal hormones, and metabolic signals are known to potentiate insulin secretion through GPCRs. We show here that β cell–specific inactivation of the genes encoding the G protein α-subunits Gαq and Gα11 resulted in impaired glucose tolerance and insulin secretion in mice. Interestingly, the defects observed in Gαq/Gα11-deficient β cells were not restricted to loss of muscarinic or metabolic potentiation of insulin release; the response to glucose per se was also diminished. Electrophysiological recordings revealed that glucose-induced depolarization of isolated β cells was impaired in the absence of Gαq/Gα11, and closure of KATP channels was inhibited. We provide evidence that this reduced excitability was due to a loss of β cell–autonomous potentiation of insulin secretion through factors cosecreted with insulin. We identified as autocrine mediators involved in this process extracellular nucleotides such as uridine diphosphate acting through the Gq/G11-coupled P2Y6 receptor and extracellular calcium acting through the calcium-sensing receptor. Thus, the Gq/G11-mediated signaling pathway potentiates insulin secretion in response to glucose by integrating systemic as well as autocrine/paracrine mediators.

Authors

Antonia Sassmann, Belinda Gier, Hermann-Josef Gröne, Gisela Drews, Stefan Offermanns, Nina Wettschureck

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