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

Cardiovascular Diabetology

Original Investigation

Weidong Chai¹  Zhenqi Liu¹  Qian Wang²  Mei-Hua Chen²  Weibin Shi³  Jing Li⁴ 

[1] Department of Medicine, University of Virginia, 22908, Charlottesville, VA, USA;Department of Radiology and Medical Imaging, University of Virginia, 22908, Charlottesville, VA, USA;Department of Radiology and Medical Imaging, University of Virginia, 22908, Charlottesville, VA, USA;Biochemistry & Molecular Genetics, University of Virginia, 22908, Charlottesville, VA, USA;Department of Radiology and Medical Imaging, University of Virginia, 22908, Charlottesville, VA, USA;School of Chemical Engineering and Technology, Tianjin University, 300072, Tianjin, China;

关键词: Insulin Secretion;    Western Diet;    Chow Diet;    Insulin Tolerance Test;    Islet Mass;   

DOI  :  10.1186/1475-2840-10-117

 received in 2011-10-07, accepted in 2011-12-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundType 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 ResultsWhen 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.ConclusionThis 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.

【 授权许可】

Unknown   
© Li et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. 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.