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Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice
Joint Authors
Heinonen, Suvi E.
Jönsson-Rylander, Ann-Cathrine
Adingupu, Damilola D.
Andréasson, Anne-Christine
Brusberg, Mikael
Ahnmark, Andrea
Behrendt, Margareta
Leighton, Brendan
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-09-28
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Aim.
Models combining diabetes and atherosclerosis are important in evaluating the cardiovascular (CV) effects and safety of antidiabetes drugs in the development of treatments targeting CV complications.
Our aim was to evaluate if crossing the heterozygous glucokinase knockout mouse (GK+/−) and hyperlipidemic mouse deficient in apolipoprotein E (ApoE−/−) will generate a disease model exhibiting a diabetic and macrovascular phenotype.
Methods.
The effects of defective glucokinase on the glucose metabolism and on the progression and regression of atherosclerosis on high-fat diets were studied in both genders of GK+/−ApoE−/− and ApoE−/− mice.
Coronary vascular function of the female GK+/−ApoE−/− and ApoE−/− mice was also investigated.
Results.
GK+/−ApoE−/− mice show a stable hyperglycemia which was increased on Western diet.
In oral glucose tolerance test, GK+/−ApoE−/− mice showed significant glucose intolerance and impaired glucose-stimulated insulin secretion.
Plasma lipids were comparable with ApoE−/− mice; nevertheless the GK+/−ApoE−/− mice showed slightly increased atherosclerosis development.
Conclusions.
The GK+/−ApoE−/− mice showed a stable and reproducible hyperglycemia, accelerated atherosclerotic lesion progression, and no lesion regression after lipid lowering.
This novel model provides a promising tool for drug discovery, enabling the evaluation of compound effects against both diabetic and cardiovascular endpoints simultaneously in one animal model.
American Psychological Association (APA)
Adingupu, Damilola D.& Heinonen, Suvi E.& Andréasson, Anne-Christine& Brusberg, Mikael& Ahnmark, Andrea& Behrendt, Margareta…[et al.]. 2016. Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice. Journal of Diabetes Research،Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1108290
Modern Language Association (MLA)
Adingupu, Damilola D.…[et al.]. Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice. Journal of Diabetes Research No. 2016 (2016), pp.1-11.
https://search.emarefa.net/detail/BIM-1108290
American Medical Association (AMA)
Adingupu, Damilola D.& Heinonen, Suvi E.& Andréasson, Anne-Christine& Brusberg, Mikael& Ahnmark, Andrea& Behrendt, Margareta…[et al.]. Hyperglycemia Induced by Glucokinase Deficiency Accelerates Atherosclerosis Development and Impairs Lesion Regression in Combined Heterozygous Glucokinase and the Apolipoprotein E-Knockout Mice. Journal of Diabetes Research. 2016. Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1108290
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108290