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Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic vascular disease, but it is unknown whether the other way around is true too. C57BL/6 (B6) and BALB/cJ (BALB) are two mouse strains that differ markedly in their susceptibility to atherosclerosis. In...

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Autores principales: Li, Jing, Wang, Qian, Chai, Weidong, Chen, Mei-Hua, Liu, Zhenqi, Shi, Weibin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273441/
https://www.ncbi.nlm.nih.gov/pubmed/22204493
http://dx.doi.org/10.1186/1475-2840-10-117
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author Li, Jing
Wang, Qian
Chai, Weidong
Chen, Mei-Hua
Liu, Zhenqi
Shi, Weibin
author_facet Li, Jing
Wang, Qian
Chai, Weidong
Chen, Mei-Hua
Liu, Zhenqi
Shi, Weibin
author_sort Li, Jing
collection PubMed
description BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic vascular disease, but it is unknown whether the other way around is true too. C57BL/6 (B6) and BALB/cJ (BALB) are two mouse strains that differ markedly in their susceptibility to atherosclerosis. In this study we investigated the development of diet-induced T2DM in these two strains. METHODS AND RESULTS: When deficient in apolipoprotein E (apoE(-/-)) and fed a Western diet for 12 weeks, atherosclerosis-susceptible B6 mice developed significant hyperglycemia. In contrast, atherosclerosis-resistant BALB apoE(-/- )mice had much lower plasma glucose levels than B6.apoE(-/- )mice on either chow or Western diet and during an intraperitoneal glucose tolerance test. In response to glucose BALB.apoE(-/- )mice displayed both the first and second phases of insulin secretion but the second phase of insulin secretion was absent in B6.apoE(-/- )mice. In response to insulin B6.apoE(-/- )mice showed a deeper and longer-lasting fall in blood glucose levels while BALB.apoE(-/- )mice showed little reduction in glucose levels. Pancreatic islet area of BALB.apoE(-/- )mice on light microscopy nearly doubled the area of B6.apoE(-/- )mice. Most circulating proinflammatory cytokines were lower in BALB.apoE(-/- )than in B6.apoE(-/- )mice on the Western diet, as determined by protein arrays. Increased macrophage infiltration in islets was observed in B6.apoE(-/- )mice by immunostaining for Mac2 and also by flow cytometry. CONCLUSION: This study demonstrates that defects in insulin secretion rather than defects in insulin resistance explain the marketed difference in susceptibility to T2DM in the B6.apoE(-/- )and BALB.apoE(-/- )mouse model. A smaller islet mass and more prominent islet inflammation may explain the vulnerability of B6.apoE(-/- )mice to diet-induced diabetes.
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spelling pubmed-32734412012-02-07 Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility Li, Jing Wang, Qian Chai, Weidong Chen, Mei-Hua Liu, Zhenqi Shi, Weibin Cardiovasc Diabetol Original Investigation BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic vascular disease, but it is unknown whether the other way around is true too. C57BL/6 (B6) and BALB/cJ (BALB) are two mouse strains that differ markedly in their susceptibility to atherosclerosis. In this study we investigated the development of diet-induced T2DM in these two strains. METHODS AND RESULTS: When deficient in apolipoprotein E (apoE(-/-)) and fed a Western diet for 12 weeks, atherosclerosis-susceptible B6 mice developed significant hyperglycemia. In contrast, atherosclerosis-resistant BALB apoE(-/- )mice had much lower plasma glucose levels than B6.apoE(-/- )mice on either chow or Western diet and during an intraperitoneal glucose tolerance test. In response to glucose BALB.apoE(-/- )mice displayed both the first and second phases of insulin secretion but the second phase of insulin secretion was absent in B6.apoE(-/- )mice. In response to insulin B6.apoE(-/- )mice showed a deeper and longer-lasting fall in blood glucose levels while BALB.apoE(-/- )mice showed little reduction in glucose levels. Pancreatic islet area of BALB.apoE(-/- )mice on light microscopy nearly doubled the area of B6.apoE(-/- )mice. Most circulating proinflammatory cytokines were lower in BALB.apoE(-/- )than in B6.apoE(-/- )mice on the Western diet, as determined by protein arrays. Increased macrophage infiltration in islets was observed in B6.apoE(-/- )mice by immunostaining for Mac2 and also by flow cytometry. CONCLUSION: This study demonstrates that defects in insulin secretion rather than defects in insulin resistance explain the marketed difference in susceptibility to T2DM in the B6.apoE(-/- )and BALB.apoE(-/- )mouse model. A smaller islet mass and more prominent islet inflammation may explain the vulnerability of B6.apoE(-/- )mice to diet-induced diabetes. BioMed Central 2011-12-28 /pmc/articles/PMC3273441/ /pubmed/22204493 http://dx.doi.org/10.1186/1475-2840-10-117 Text en Copyright ©2011 Li et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Investigation
Li, Jing
Wang, Qian
Chai, Weidong
Chen, Mei-Hua
Liu, Zhenqi
Shi, Weibin
Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title_full Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title_fullStr Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title_full_unstemmed Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title_short Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
title_sort hyperglycemia in apolipoprotein e-deficient mouse strains with different atherosclerosis susceptibility
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273441/
https://www.ncbi.nlm.nih.gov/pubmed/22204493
http://dx.doi.org/10.1186/1475-2840-10-117
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