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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

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dc.contributor.authorOh, Y S-
dc.contributor.authorKhil, L-Y-
dc.contributor.authorCho, K A-
dc.contributor.authorRyu, S J-
dc.contributor.authorHa, M K-
dc.contributor.authorCheon, G J-
dc.contributor.authorLee, T S-
dc.contributor.authorYoon, J-W-
dc.contributor.authorJun, H-S-
dc.contributor.authorPark, S C-
dc.date.accessioned2010-06-07T03:29:11Z-
dc.date.available2010-06-07T03:29:11Z-
dc.date.issued2008-04-15-
dc.identifier.citationDiabetologia 51(6):1025-1034en
dc.identifier.issn0012-186X (Print)-
dc.identifier.urihttp://www.springerlink.com/content/q485m1k10q73nq76/fulltext.pdf-
dc.identifier.urihttps://hdl.handle.net/10371/67499-
dc.description.abstractAIMS/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.en
dc.language.isoenen
dc.publisherSpringer Verlagen
dc.subjectAging/*physiologyen
dc.subjectAnimalsen
dc.subjectBiological Transporten
dc.subjectBlood Glucose/drug effects/metabolismen
dc.subjectCaveolin 1/*physiologyen
dc.subjectCrosses, Geneticen
dc.subjectDiabetes Mellitus, Type 2/*physiopathologyen
dc.subjectDisease Models, Animalen
dc.subjectFemaleen
dc.subjectFluorodeoxyglucose F18/metabolismen
dc.subjectGlucose Tolerance Testen
dc.subjectInsulin/pharmacologyen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Inbred C57BLen
dc.subjectMice, Inbred DBAen
dc.subjectMuscle, Skeletal/*physiopathologyen
dc.subjectPositron-Emission Tomographyen
dc.titleA 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 modelen
dc.typeArticleen
dc.identifier.doi10.1007/s00125-008-0993-0-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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