GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells

Abstract Diabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling...

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Autores principales:	Jonathan Snyder, Atreju I Lackey, G. Schuyler Brown, Melisa Diaz, Tian Yuzhen, Priscila Y. Sato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af1b5d05e31540d9b993ae13c398778d
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spelling	oai:doaj.org-article:af1b5d05e31540d9b993ae13c398778d2021-12-02T15:49:53ZGRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells10.1038/s41598-021-90253-z2045-2322https://doaj.org/article/af1b5d05e31540d9b993ae13c398778d2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90253-zhttps://doaj.org/toc/2045-2322Abstract Diabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling. GPCR kinase 2 (GRK2), a key regulator of GPCRs, is reported to be downregulated in the pancreas of spontaneously obesogenic and diabetogenic mice (ob/ob). Moreover, recent studies have shown that GRK2 non-canonically localizes to the cardiac mitochondrion, where it can contribute to glucose metabolism. Thus, islet GRK2 may impact insulin secretion through either mechanism. Utilizing Min6 cells, a pancreatic ß-cell model, we knocked down GRK2 and measured glucose-mediated intracellular calcium responses and insulin secretion. Silencing of GRK2 attenuated calcium responses, which were rescued by pertussis toxin pre-treatment, suggesting a Gαi/o-dependent mechanism. Pancreatic deletion of GRK2 in mice resulted in glucose intolerance with diminished insulin secretion. These differences were due to diminished insulin release rather than decreased insulin content or gross differences in islet architecture. Furthermore, a high fat diet feeding regimen exacerbated the metabolic phenotype in this model. These results suggest a new role for pancreatic islet GRK2 in glucose-mediated insulin responses that is relevant to type 2 diabetes disease progression.Jonathan SnyderAtreju I LackeyG. Schuyler BrownMelisa DiazTian YuzhenPriscila Y. SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan Snyder Atreju I Lackey G. Schuyler Brown Melisa Diaz Tian Yuzhen Priscila Y. Sato GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
description	Abstract Diabetes is a metabolic syndrome rooted in impaired insulin and/or glucagon secretory responses within the pancreatic islets of Langerhans (islets). Insulin secretion is primarily regulated by two key factors: glucose-mediated ATP production and G-protein coupled receptors (GPCRs) signaling. GPCR kinase 2 (GRK2), a key regulator of GPCRs, is reported to be downregulated in the pancreas of spontaneously obesogenic and diabetogenic mice (ob/ob). Moreover, recent studies have shown that GRK2 non-canonically localizes to the cardiac mitochondrion, where it can contribute to glucose metabolism. Thus, islet GRK2 may impact insulin secretion through either mechanism. Utilizing Min6 cells, a pancreatic ß-cell model, we knocked down GRK2 and measured glucose-mediated intracellular calcium responses and insulin secretion. Silencing of GRK2 attenuated calcium responses, which were rescued by pertussis toxin pre-treatment, suggesting a Gαi/o-dependent mechanism. Pancreatic deletion of GRK2 in mice resulted in glucose intolerance with diminished insulin secretion. These differences were due to diminished insulin release rather than decreased insulin content or gross differences in islet architecture. Furthermore, a high fat diet feeding regimen exacerbated the metabolic phenotype in this model. These results suggest a new role for pancreatic islet GRK2 in glucose-mediated insulin responses that is relevant to type 2 diabetes disease progression.
format	article
author	Jonathan Snyder Atreju I Lackey G. Schuyler Brown Melisa Diaz Tian Yuzhen Priscila Y. Sato
author_facet	Jonathan Snyder Atreju I Lackey G. Schuyler Brown Melisa Diaz Tian Yuzhen Priscila Y. Sato
author_sort	Jonathan Snyder
title	GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
title_short	GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
title_full	GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
title_fullStr	GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
title_full_unstemmed	GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
title_sort	grk2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af1b5d05e31540d9b993ae13c398778d
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GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells

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