TY - JOUR
T1 - Apolipoprotein e deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus
AU - Kawashima, Y.
AU - Chen, J.
AU - Sun, H.
AU - Lann, D.
AU - Hajjar, R. J.
AU - Yakar, S.
AU - LeRoith, D.
N1 - Funding Information:
Acknowledgements We thank N. Mall (Mt Sinai School of Medicine, New York) for help with histological experiments, and W. Jou and O. Gavrilova (NIDDK, Bethesda, MD, USA) for assistance with liver triacylglycerol assays. This study was supported by an American Diabetes Association Mentorship Grant, awarded to Y. Kawashima and D. LeRoith.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - ApoE gene deletion
KW - Atherosclerosis
KW - MKR mouse model of type 2 diabetes
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U2 - 10.1007/s00125-009-1378-8
DO - 10.1007/s00125-009-1378-8
M3 - Article
C2 - 19436992
AN - SCOPUS:67349280145
SN - 0012-186X
VL - 52
SP - 1434
EP - 1441
JO - Diabetologia
JF - Diabetologia
IS - 7
ER -
