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Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice

The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT) deletion mutation, a widely used model of diet-induced obesity...

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Autores principales: Roat, Regan, Rao, Vandana, Doliba, Nicolai M., Matschinsky, Franz M., Tobias, John W., Garcia, Eden, Ahima, Rexford S., Imai, Yumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914796/
https://www.ncbi.nlm.nih.gov/pubmed/24505268
http://dx.doi.org/10.1371/journal.pone.0086815
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author Roat, Regan
Rao, Vandana
Doliba, Nicolai M.
Matschinsky, Franz M.
Tobias, John W.
Garcia, Eden
Ahima, Rexford S.
Imai, Yumi
author_facet Roat, Regan
Rao, Vandana
Doliba, Nicolai M.
Matschinsky, Franz M.
Tobias, John W.
Garcia, Eden
Ahima, Rexford S.
Imai, Yumi
author_sort Roat, Regan
collection PubMed
description The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT) deletion mutation, a widely used model of diet-induced obesity and diabetes. On high fat diet (HF), the mice developed obesity and hyperinsulinemia, while blood glucose levels were only mildly elevated indicating a substantial capacity to compensate for insulin resistance. The basal serum insulin levels were elevated in HF mice, but insulin secretion in response to glucose load was significantly blunted. Hyperinsulinemia in HF fed mice was associated with an increase in islet mass and size along with higher BrdU incorporation to β cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS) of isolated islets were comparable in HF and normal chow fed mice. Islets isolated from HF fed mice had elevated basal oxygen consumption per islet but failed to increase oxygen consumption further in response to glucose or carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP). To obtain an unbiased assessment of metabolic pathways in islets, we performed microarray analysis comparing gene expression in islets from HF to normal chow-fed mice. A few genes, for example, those genes involved in the protection against oxidative stress (hypoxia upregulated protein 1) and Pgc1α were up-regulated in HF islets. In contrast, several genes in extracellular matrix and other pathways were suppressed in HF islets. These results indicate that islets from C57BL/6J mice with NNT deletion mutation develop structural, metabolic and gene expression features consistent with compensation and decompensation in response to HF diet.
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spelling pubmed-39147962014-02-06 Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice Roat, Regan Rao, Vandana Doliba, Nicolai M. Matschinsky, Franz M. Tobias, John W. Garcia, Eden Ahima, Rexford S. Imai, Yumi PLoS One Research Article The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT) deletion mutation, a widely used model of diet-induced obesity and diabetes. On high fat diet (HF), the mice developed obesity and hyperinsulinemia, while blood glucose levels were only mildly elevated indicating a substantial capacity to compensate for insulin resistance. The basal serum insulin levels were elevated in HF mice, but insulin secretion in response to glucose load was significantly blunted. Hyperinsulinemia in HF fed mice was associated with an increase in islet mass and size along with higher BrdU incorporation to β cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS) of isolated islets were comparable in HF and normal chow fed mice. Islets isolated from HF fed mice had elevated basal oxygen consumption per islet but failed to increase oxygen consumption further in response to glucose or carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP). To obtain an unbiased assessment of metabolic pathways in islets, we performed microarray analysis comparing gene expression in islets from HF to normal chow-fed mice. A few genes, for example, those genes involved in the protection against oxidative stress (hypoxia upregulated protein 1) and Pgc1α were up-regulated in HF islets. In contrast, several genes in extracellular matrix and other pathways were suppressed in HF islets. These results indicate that islets from C57BL/6J mice with NNT deletion mutation develop structural, metabolic and gene expression features consistent with compensation and decompensation in response to HF diet. Public Library of Science 2014-02-05 /pmc/articles/PMC3914796/ /pubmed/24505268 http://dx.doi.org/10.1371/journal.pone.0086815 Text en © 2014 Roat et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roat, Regan
Rao, Vandana
Doliba, Nicolai M.
Matschinsky, Franz M.
Tobias, John W.
Garcia, Eden
Ahima, Rexford S.
Imai, Yumi
Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title_full Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title_fullStr Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title_full_unstemmed Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title_short Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice
title_sort alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese c57bl/6j mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914796/
https://www.ncbi.nlm.nih.gov/pubmed/24505268
http://dx.doi.org/10.1371/journal.pone.0086815
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