Genetic background (C57BL/6J Versus FVB/N) strongly influences the severity of diabetes and insulin resistance in ob/ob mice

Martin Haluzik, Carlo Colombo, Oksana Gavrilova, Streamson Chua, Nicole Wolf, Min Chen, Bethel Stannard, Kelly R. Dietz, Derek Le Roith, Marc L. Reitman

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

We studied the effects of genetic background on the phenotype of ob/ob mice, a model of severe obesity, insulin resistance, and diabetes caused by leptin deficiency. Despite a comparable degree of obesity and hyperinsulinemia, C57BL/6J ob/ob mice had much milder hyperglycemia and, surprisingly, normal circulating adiponectin levels despite still-prominent signs of insulin resistance. Hyperinsulinemic-euglycemic clamp revealed relatively less whole-body and muscle insulin resistance in C57BL/6J ob/ob mice, whereas liver insulin resistance tended to be more severe than in FVB/N ob/ob mice. C57BL/6J ob/ob mice had also more rapid clearance of circulating triglycerides and more severe hepatic steatosis. We suggest that strain-related distinction in lipid handling is the most important player in the differences in diabetic phenotype and insulin sensitivity, whereas the impact of circulating adiponectin levels on the overall phenotype of ob/ob mice is less important.

Original languageEnglish (US)
Pages (from-to)3258-3264
Number of pages7
JournalEndocrinology
Volume145
Issue number7
DOIs
StatePublished - Jul 2004

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