Alterations in brain hexokinase activity associated with streptozotocin-induced diabetes mellitus in the rat

Abstract

The effects of streptozotocin-induced diabetes mellitus on the activity of discrete regions of the brain were studied with histochemical localization and photodensitometric quantification of the metabolic enzyme, hexokinase. Two weeks after a single injection of streptozotocin (65 mg/kg, i.p.), plasma glucose and osmolarity levels were elevated, and plasma sodium concentrations were depressed. These changes were reversed in diabetic rats treated with insulin. Accompanying these symptoms of diabetes were significant increases in hexokinase activity in the magnocellular division of the paraventricular nucleus of the hypothalamus (mPVH, 12.1%), the medial subdivision of the nucleus of the tractus solitarius (mNTS, 15.5%), and the commissural subdivision of the NTS (cNTS, 10.9%). An increase, though just below the level of significance, was also observed in the supraoptic nucleus of the hypothalamus (SON, 11.5%). The increases in hexokinase activity were completely reversed in the cNTS (and SON) and only partly reversed in the mPVH and mNTS of insulin-treated diabetic rats. No changes in hexokinase activity were seen in the subfornical organ, medial preoptic area, parvocellular division of the PVH, locus coeruleus, or dorsal motor nucleus of the vagus of diabetic rats. These results reinforce the idea that the brain is not exempt from changes associated with diabetes mellitus and suggest that metabolic alterations in the mPVH (and SON) and two divisions of the NTS are likely related to changes in vasopressin production and blood volume, respectively.