Publications
Detailed Information
A potential role for skeletal muscle caveolin-1 as an insulin sensitivity modulator in ageing-dependent non-obese type 2 diabetes: studies in a new mouse model
Cited 35 time in
Web of Science
Cited 38 time in Scopus
- Authors
- Issue Date
- 2008-04-15
- Publisher
- Springer Verlag
- Citation
- Diabetologia 51(6):1025-1034
- Keywords
- Aging/*physiology ; Animals ; Biological Transport ; Blood Glucose/drug effects/metabolism ; Caveolin 1/*physiology ; Crosses, Genetic ; Diabetes Mellitus, Type 2/*physiopathology ; Disease Models, Animal ; Female ; Fluorodeoxyglucose F18/metabolism ; Glucose Tolerance Test ; Insulin/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Muscle, Skeletal/*physiopathology ; Positron-Emission Tomography
- Abstract
- AIMS/HYPOTHESIS: Type 2 diabetes mellitus is a common age-dependent disease. We discovered that male offspring of non-diabetic C57BL/6 and DBA/2 mice, called JYD mice, develop type 2 diabetes when they grow old. JYD mice show characteristics of insulin resistance, hyperglycaemia and hyperinsulinaemia in old age without obesity. We postulated that the mechanism of age-dependent type 2 diabetes in this model relates to caveolin-1 status in skeletal muscle, which appears to regulate insulin sensitivity in the mice. METHODS: We compared insulin sensitivity in aged C57BL/6 and JYD mice using glucose and insulin tolerance tests and (18)F-fluorodeoxyglucose positron emission tomography. We also determined insulin signalling molecules and caveolin proteins using western blotting, and altered caveolin-1 levels in skeletal muscle of C57BL/6 and JYD mice using viral vector systems, to examine the effect of this on insulin sensitivity. RESULTS: In 30-week-old C57BL/6 and JYD mice, the basal levels of IRS-1, Akt and peroxisome proliferator-activated receptor-gamma decreased, as did insulin-stimulated phosphorylation of Akt and insulin receptor beta. However, caveolin-1 was only increased about twofold in 30-week-old JYD mice as compared with 3-week-old mice, whereas an eightfold increase was seen in C57BL/6 mice. Downregulation of caveolin-1 production in C57BL/6 mice caused severe impairment of glucose and insulin tolerance. Upregulation of caveolin-1 in aged diabetic JYD mice significantly improved insulin sensitivity with a concomitant increase of glucose uptake in the skeletal muscle. CONCLUSIONS/INTERPRETATION: The level of skeletal muscle caveolin-1 is correlated with the progression of age-dependent type 2 diabetes in JYD mice.
- ISSN
- 0012-186X (Print)
- Language
- English
- URI
- http://www.springerlink.com/content/q485m1k10q73nq76/fulltext.pdf
https://hdl.handle.net/10371/67499
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.