Abstract
The turnover of phosphoinositides as well as Na,K-ATPase and protein kinase C (PKC) activities and levels of PKCα were examined in the Zucker diabetic fatty rat (ZDF/GMI-fa), a recently described model for non-insulin dependent diabetes mellitus. These animals exhibit serum glucose concentrations greater than 450 mg/dl after 10 weeks of age. As compared to age matched lean controls, the proportion of 32P incorporated into phosphatidylinositol-4,5-bisphosphate (PIP2) increased from 36 to 43 percent. in obese male ZDF rats which had been diabetic for 2–4 months. Other phospholipids showed no change or small decreases. When these data are expressed as quantity of isotope incorporated, only PIP2 showed a consistent increase. Nerve Na,K-ATPase activity was reduced by 32% in animals after diabetes of this duration. These alterations resemble those observed in several other animal models of diabetes. PKC activity was diminished in a detergent extracted membrane fraction from diabetic nerve, but was unchanged in a cytosolic fraction. The expression of PKCα in diabetic nerve was reduced by 47% and underwent a redistribution from a membrane-associated to a soluble form. © 1997 John Wiley & Sons, Ltd.
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