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G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion

Elevated fasting blood glucose (FBG) is associated with increased risk for the development of type 2 diabetes and cardiovascular-associated mortality. Genome-wide association studies (GWAS) have linked polymorphisms in G6PC2 with variations in FBG and body fat, although not insulin sensitivity or gl...

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Autores principales: Pound, Lynley D., Oeser, James K., O’Brien, Tracy P., Wang, Yingda, Faulman, Chandler J., Dadi, Prasanna K., Jacobson, David A., Hutton, John C., McGuinness, Owen P., Shiota, Masakazu, O’Brien, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636628/
https://www.ncbi.nlm.nih.gov/pubmed/23274894
http://dx.doi.org/10.2337/db12-1067
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author Pound, Lynley D.
Oeser, James K.
O’Brien, Tracy P.
Wang, Yingda
Faulman, Chandler J.
Dadi, Prasanna K.
Jacobson, David A.
Hutton, John C.
McGuinness, Owen P.
Shiota, Masakazu
O’Brien, Richard M.
author_facet Pound, Lynley D.
Oeser, James K.
O’Brien, Tracy P.
Wang, Yingda
Faulman, Chandler J.
Dadi, Prasanna K.
Jacobson, David A.
Hutton, John C.
McGuinness, Owen P.
Shiota, Masakazu
O’Brien, Richard M.
author_sort Pound, Lynley D.
collection PubMed
description Elevated fasting blood glucose (FBG) is associated with increased risk for the development of type 2 diabetes and cardiovascular-associated mortality. Genome-wide association studies (GWAS) have linked polymorphisms in G6PC2 with variations in FBG and body fat, although not insulin sensitivity or glucose tolerance. G6PC2 encodes an islet-specific, endoplasmic reticulum–resident glucose-6-phosphatase catalytic subunit. A combination of in situ perfused pancreas, in vitro isolated islet, and in vivo analyses were used to explore the function of G6pc2 in mice. G6pc2 deletion had little effect on insulin sensitivity and glucose tolerance, whereas body fat was reduced in female G6pc2 knockout (KO) mice on both a chow and high-fat diet, observations that are all consistent with human GWAS data. G6pc2 deletion resulted in a leftward shift in the dose-response curve for glucose-stimulated insulin secretion (GSIS). As a consequence, under fasting conditions in which plasma insulin levels were identical, blood glucose levels were reduced in G6pc2 KO mice, again consistent with human GWAS data. Glucose-6-phosphatase activity was reduced, whereas basal cytoplasmic calcium levels were elevated in islets isolated from G6pc2 KO mice. These data suggest that G6pc2 represents a novel, negative regulator of basal GSIS that acts by hydrolyzing glucose-6-phosphate, thereby reducing glycolytic flux.
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spelling pubmed-36366282014-05-01 G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion Pound, Lynley D. Oeser, James K. O’Brien, Tracy P. Wang, Yingda Faulman, Chandler J. Dadi, Prasanna K. Jacobson, David A. Hutton, John C. McGuinness, Owen P. Shiota, Masakazu O’Brien, Richard M. Diabetes Original Research Elevated fasting blood glucose (FBG) is associated with increased risk for the development of type 2 diabetes and cardiovascular-associated mortality. Genome-wide association studies (GWAS) have linked polymorphisms in G6PC2 with variations in FBG and body fat, although not insulin sensitivity or glucose tolerance. G6PC2 encodes an islet-specific, endoplasmic reticulum–resident glucose-6-phosphatase catalytic subunit. A combination of in situ perfused pancreas, in vitro isolated islet, and in vivo analyses were used to explore the function of G6pc2 in mice. G6pc2 deletion had little effect on insulin sensitivity and glucose tolerance, whereas body fat was reduced in female G6pc2 knockout (KO) mice on both a chow and high-fat diet, observations that are all consistent with human GWAS data. G6pc2 deletion resulted in a leftward shift in the dose-response curve for glucose-stimulated insulin secretion (GSIS). As a consequence, under fasting conditions in which plasma insulin levels were identical, blood glucose levels were reduced in G6pc2 KO mice, again consistent with human GWAS data. Glucose-6-phosphatase activity was reduced, whereas basal cytoplasmic calcium levels were elevated in islets isolated from G6pc2 KO mice. These data suggest that G6pc2 represents a novel, negative regulator of basal GSIS that acts by hydrolyzing glucose-6-phosphate, thereby reducing glycolytic flux. American Diabetes Association 2013-05 2013-04-16 /pmc/articles/PMC3636628/ /pubmed/23274894 http://dx.doi.org/10.2337/db12-1067 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Pound, Lynley D.
Oeser, James K.
O’Brien, Tracy P.
Wang, Yingda
Faulman, Chandler J.
Dadi, Prasanna K.
Jacobson, David A.
Hutton, John C.
McGuinness, Owen P.
Shiota, Masakazu
O’Brien, Richard M.
G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title_full G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title_fullStr G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title_full_unstemmed G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title_short G6PC2: A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
title_sort g6pc2: a negative regulator of basal glucose-stimulated insulin secretion
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636628/
https://www.ncbi.nlm.nih.gov/pubmed/23274894
http://dx.doi.org/10.2337/db12-1067
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