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.

Diabetologia
Y S OhS C Park

Abstract

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. 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. 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 eight...Continue Reading

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