| First Author | Kawashima Y | Year | 2009 |
| Journal | Diabetologia | Volume | 52 |
| Issue | 7 | Pages | 1434-41 |
| PubMed ID | 19436992 | Mgi Jnum | J:166108 |
| Mgi Id | MGI:4839713 | Doi | 10.1007/s00125-009-1378-8 |
| Citation | Kawashima Y, et al. (2009) Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus. Diabetologia 52(7):1434-41 |
| abstractText | 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. |
