title: Hyperglycemia and hyperlipidemia are associated with endothelial dysfunction during the development of type 2 diabetes.
abstract: Diabetes mellitus impairs endothelial function, which can be considered as the hallmark in the development of cardiovascular diseases. Hyperglycemia, hyperinsulinemia, and hyperlipidemia are believed to contribute to endothelial dysfunction. In the present study, we investigated the possible links among these plasma metabolic markers and endothelial function in a mouse model during the development of type 2 diabetes. C57BL/6J-Lepob/ob mice at 8, 12, and 16 weeks were used to study endothelial function during the establishment of type 2 diabetes. Endothelial function was accessed in vitro in the thoracic aorta by measuring acetylcholine (ACh)-stimulated vasodilatation. Blood plasma was obtained for the measurements of glucose, insulin, triglycerides, and cholesterol levels. Correlation and multiple regression analysis revealed strong negative associations between the ACh responsiveness and the plasma levels of glucose, insulin, and lipid profiles at the age of 8 weeks. Associations were observed at neither older age nor in C57BL/6J mice. In conclusion, the increase in plasma levels of glucose, insulin, and lipids is associated with the impairment of the endothelial function during the early stage of the development of type 2 diabetes. The loss of correlation at an older age suggests multifactorial regulation of endothelial function and cardiovascular complications at later stages of the disease.
authors.affiliation: James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, 1081 Burrard Street, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada. eokon@mrl.ubc.ca
authors.forename: Elena B
authors.initials: EB
authors.lastname: Okon
authors.forename: Ada W Y
authors.initials: AW
authors.lastname: Chung
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006943:Hyperglycemia / Q000503:physiopathology*; D006949:Hyperlipidemias / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D014665:Vasodilator Agents; D002784:Cholesterol; D000109:Acetylcholine