Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus.
OBJECTIVE
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
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.
Division of Endocrinology, Diabetes, and Bone Diseases, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.
Y
Y
Kawashima
J
J
Chen
H
H
Sun
D
D
Lann
R J
RJ
Hajjar
S
S
Yakar
D
D
Leroith
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002791:Cholesterol, Dietary / Q000097:blood / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D001786:Blood Glucose; D002791:Cholesterol, Dietary; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides