Conformation changes in brain calcineurin in diabetic rats with or withouttreatment with vanadyl sulfate

Recent studies have shown that vanadium salts are able to reduce blood gluc ose in diabetics and overcome, to some degree, insulin resistance. This par adigm has been followed to monitor the effects of diabetes and vanadyl trea tment on brain calcineurin (CN), an important protein phosphatase. Male rat s were rendered diabetic by a single injection of streptozotocin (STZ), res ulting in an elevation of blood glucose from 108 +/- 13 to >400 mg/dl. Diab etic animals were given vanadyl sulfate trihydrate (0.5 mg/dl.) in their dr inking water for 3 weeks, which led to a fall in blood glucose to 156 +/- 5 3 mg/ml. Brain CN activity (units/mg brain protein) in diabetic rats was 77 % that of control animals, whereas vanadyl-treated diabetic animals were ch aracterized by CN activities like that of controls. CN was purified from br ains of control animals, STZ-induced diabetic animals, and STZ-induced diab etic animals receiving vanadyl, then spin-labeled with 3-maleimide-proxyl a nd studied via electron spin resonance spectroscopy. The rotational correla tion time of CN from control animals and vanadyl-treated diabetic animals w as 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 increas e in the rotational correlation time of brain CN relative to control animal s, yet vanadyl treatment of STZ-induced diabetic animals reduced the rotati onal correlation time to that of control. These data suggest that diabetes can lead to apparent conformational changes in brain CN; also, CN conformat ion in diabetic rats was restored by vanadyl treatment.