S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biochemistry & Molecular Biology (생화학교실) Journal Papers (저널논문_생화학교실)
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
- Oh, Y S; Khil, L-Y; Cho, K A; Ryu, S J; Ha, M K; Cheon, G J; Lee, T S; Yoon, J-W; Jun, H-S; Park, S C
- Issue Date
- Springer Verlag
- Diabetologia 51(6):1025-1034
- 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
- 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.
- 0012-186X (Print)
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