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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 33 time in Web of Science Cited 36 time in Scopus
Authors
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
2008-04-15
Publisher
Springer Verlag
Citation
Diabetologia 51(6):1025-1034
Keywords
Aging/*physiologyAnimalsBiological TransportBlood Glucose/drug effects/metabolismCaveolin 1/*physiologyCrosses, GeneticDiabetes Mellitus, Type 2/*physiopathologyDisease Models, AnimalFemaleFluorodeoxyglucose F18/metabolismGlucose Tolerance TestInsulin/pharmacologyMaleMiceMice, Inbred C57BLMice, Inbred DBAMuscle, Skeletal/*physiopathologyPositron-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
DOI
https://doi.org/10.1007/s00125-008-0993-0
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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