Conformation changes in brain calcineurin in diabetic rats with or without treatment with vanadyl sulfate.

Abstract

Recent studies have shown that vanadium salts are able to reduce blood glucose in diabetics and overcome, to some degree, insulin resistance. This paradigm has been followed to monitor the effects of diabetes and vanadyl treatment on brain calcineurin (CN), an important protein phosphatase. Male rats were rendered diabetic by a single injection of streptozotocin (STZ), resulting in an elevation of blood glucose from 108 +/- 13 to >400 mg/dl. Diabetic animals were given vanadyl sulfate trihydrate (0.5 mg/dl.) in their drinking water for 3 weeks, which led to a fall in blood glucose to 156 +/- 53 mg/ml. Brain CN activity (units/mg brain protein) in diabetic rats was 77% that of control animals, whereas vanadyl-treated diabetic animals were characterized by CN activities like that of controls. CN was purified from brains of control animals, STZ-induced diabetic animals, and STZ-induced diabetic animals receiving vanadyl, then spin-labeled with 3-maleimide-proxyl and studied via electron spin resonance spectroscopy. The rotational correlation time of CN from control animals and vanadyl-treated diabetic animals was 6.4 x 10(-11) s(-1), whereas that from STZ-induced-diabetic animals was 8 x 10(-11) s(-1). Thus, STZ-induced diabetes in rats results in an increase in the rotational correlation time of brain CN relative to control animals, yet vanadyl treatment of STZ-induced diabetic animals reduced the rotational correlation time to that of control. These data suggest that diabetes can lead to apparent conformational changes in brain CN; also, CN conformation in diabetic rats was restored by vanadyl treatment.