Diabetes complications in congenic leptin receptor deficient BBDR.cg‐lepr.cp rats (1072.6)

Abstract

Diabetes is a chronic disease that is associated with devastating complications. Here, we characterize micro‐ and macrovascular changes in a novel congenic BBDR.cg‐lepr.cp rat line, generated by introgression of the Koletsky leptin receptor mutation onto BioBreeding Diabetes Resistant rats. Interestingly, two subgroups of male BBDR.cg‐lepr.cp rats could be distinguished based on their blood glucose (BG), one severely diabetic (D) and one with moderately (M) elevated BG. Both groups were obese and showed significant enlargement of liver, heart and kidneys when compared to control littermates. Serum insulin, leptin, triglycerides and cholesterol were increased in all BBDR.cg‐lepr.cp rats when compared to controls, but with significant differences between groups; triglycerides and cholesterol were higher in D rats, leptin and insulin were higher in M rats. Albumin/creatinine ratio was dramatically increased and histological examination of kidneys revealed dilated and filled tubuli and loss of glomerular podocin expression, this was more pronounced in D rats when compared to M rats. All BBDR.cg‐lepr.cp rats had significantly higher systolic blood pressure, but surprisingly only M rats had increased aortic mRNA expression of endothelial activation and inflammatory markers. Collectively, our results point to different underlying factors for micro‐ and macrovascular disease in diabetes.Grant Funding Source: Supported by VR 2011‐3900; the SUMMIT consortium (IMI‐2008/115006), Påhlsson and Diabetes Found.