Apolipoprotein e deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus

Y. Kawashima, J. Chen, H. Sun, D. Lann, R. J. Hajjar, S. Yakar, D. LeRoith

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Aims/hypothesis: Although it is known that lipid metabolism plays a role in insulin resistance in type 2 diabetes and in obesity, the mechanism is still largely unknown. Apolipoprotein E (ApoE) regulates plasma lipid levels and also plays a role in the uptake of lipids into various tissues. To investigate whether the suppression of whole-particle lipoprotein uptake into tissues affects insulin responsiveness and the diabetic condition, we examined the effect of an ApoE (also known as Apoe) gene deletion in MKR mice, a mouse model of type 2 diabetes. Methods: ApoE -/- , MKR, ApoE -/- /MKR and control mice were placed on a high-fat, high-cholesterol diet for 16 weeks. Glucose tolerance, serum insulin, blood glucose, insulin tolerance, tissue triacylglycerol content and atherosclerotic lesions were assessed. Results: ApoE -/- /MKR and ApoE -/- mice showed significantly improved blood glucose, glucose tolerance and insulin sensitivity. Reduced triacylglycerol content in liver and reduced fat accumulation in liver and adipose tissue were found in ApoE -/- /MKR and ApoE -/- mice compared with control and MKR mice. ApoE -/- and ApoE -/- /MKR mice demonstrated similarly large atherosclerotic lesions, whereas MKR and control mice had small atherosclerotic lesions. Conclusions/interpretation: We demonstrated that ApoE deficiency abrogates insulin resistance in a mouse model of type 2 diabetes, suggesting that lipid accumulation in tissue is a major cause of insulin resistance in this mouse model.

Original languageEnglish (US)
Pages (from-to)1434-1441
Number of pages8
JournalDiabetologia
Volume52
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Keywords

  • ApoE gene deletion
  • Atherosclerosis
  • MKR mouse model of type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kawashima, Y., Chen, J., Sun, H., Lann, D., Hajjar, R. J., Yakar, S., & LeRoith, D. (2009). Apolipoprotein e deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus. Diabetologia, 52(7), 1434-1441. https://doi.org/10.1007/s00125-009-1378-8