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

• Main Authors: Li Jing, Wang Qian, Chai Weidong, Chen Mei-Hua, Liu Zhenqi, Shi Weibin
• Format: Article
• Language: English
• Published: BMC 2011-12-01
• Series: Cardiovascular Diabetology
• Online Access: http://www.cardiab.com/content/10/1/117

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods and Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>