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

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.

• Authors: Y Kawashima, J Chen, H Sun, D Lann, R J Hajjar, S Yakar, D Leroith
• Journal: Diabetologia (Diabetologia) Vol. 52 Issue 7 Pg. 1434-41 (Jul 2009) ISSN: 1432-0428 [Electronic] Germany
• PMID: 19436992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Blood Glucose
• Cholesterol, Dietary
• Fatty Acids, Nonesterified
• Insulin
• Triglycerides

Topics

• Adipose Tissue (metabolism)
• Animals
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (metabolism, physiopathology)
• Blood Glucose (metabolism)
• Body Composition (physiology)
• Body Weight (physiology)
• Cholesterol, Dietary (blood, pharmacology)
• Diabetes Mellitus, Type 2 (metabolism, physiopathology)
• Diabetic Angiopathies (metabolism, physiopathology)
• Disease Models, Animal
• Fatty Acids, Nonesterified (blood)
• Female
• Insulin (blood)
• Insulin Resistance (physiology)
• Lipid Metabolism (physiology)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred Strains
• Mice, Mutant Strains
• Triglycerides (blood)