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, Shoshana Yakar, D. LeRoith

Research output: Contribution to journalArticle

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 2009

Fingerprint

Apolipoproteins
Apolipoproteins E
Type 2 Diabetes Mellitus
Insulin Resistance
Insulin
Lipids
Blood Glucose
Triglycerides
Glucose
Liver
Gene Deletion
High Fat Diet
Lipid Metabolism
Lipoproteins
Adipose Tissue
Obesity
Fats
Cholesterol

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Apolipoprotein e deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus. / Kawashima, Y.; Chen, J.; Sun, H.; Lann, D.; Hajjar, R. J.; Yakar, Shoshana; LeRoith, D.

In: Diabetologia, Vol. 52, No. 7, 07.2009, p. 1434-1441.

Research output: Contribution to journalArticle

Kawashima, Y. ; Chen, J. ; Sun, H. ; Lann, D. ; Hajjar, R. J. ; Yakar, Shoshana ; LeRoith, D. / Apolipoprotein e deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus. In: Diabetologia. 2009 ; Vol. 52, No. 7. pp. 1434-1441.
@article{f04c5a13fd724f77926343ca48bebb46,
title = "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.",
keywords = "ApoE gene deletion, Atherosclerosis, MKR mouse model of type 2 diabetes",
author = "Y. Kawashima and J. Chen and H. Sun and D. Lann and Hajjar, {R. J.} and Shoshana Yakar and D. LeRoith",
year = "2009",
month = "7",
doi = "10.1007/s00125-009-1378-8",
language = "English (US)",
volume = "52",
pages = "1434--1441",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "7",

}

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, Shoshana

AU - LeRoith, D.

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

UR - http://www.scopus.com/inward/record.url?scp=67349280145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349280145&partnerID=8YFLogxK

U2 - 10.1007/s00125-009-1378-8

DO - 10.1007/s00125-009-1378-8

M3 - Article

VL - 52

SP - 1434

EP - 1441

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

ER -