Brain glutamate dehydrogenase changes in streptozotocin diabetic rats as a function of age

Abstract

SUMMARYKinetic parameters of brain glutamate dehydrogenase (GDH) were compared in the brain stem, cerebellum and cerebral cortex of three weeks and one year old streptozotocin (STZ) induced four day diabetic rats with respective controls. A single intrafemoral dose of STZ (60mg/Kg body weight) was administered to induce diabetes in both age groups. After four days the blood glucose levels showed a significant increase in the diabetic animals of both age groups compared with the respective controls. The increase in blood glucose was significant in one year old compared to the three weeks old diabetic rats. The Vm~, of the enzyme was decreased in all the brain regions studied, of the three weeks old diabetic rats without any significant change in the Kin. In the adult the Vm~x of GDH was increased in cerebellum and brain stem but was unchanged in the cerebral cortex. The K~ was unchanged in cerebellum and cerebral cortex but was increased in the brain stem. These results suggest there may be an important regulatory role of the glutamate pathway in brain neural network disturbances and neuronal degeneration in diabetes as a function of age.

Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease

“…AD is associated with progressive brain insulin resistance in the absence of T2DM, obesity, or peripheral insulin resistance (5, 6,31,32), and the molecular, biochemical, and signal transduction abnormalities in AD are virtually identical to those that occur in both T1DM and T2DM (5, 6,35,[91][92][93][94][95]. This hypothesis is supported by experimental studies in which, the administration of intracerebroventricular streptozotocin, a glucosaminenitrosourea pro-diabetes compound, resulted in cognitive impairment with deficits in spatial learning and memory, brain insulin resistance and insulin deficiency, and AD-type neurodegeneration, but not diabetes mellitus (19,(96)(97)(98)(99). In contrast, parenteral administration of streptozotocin causes diabetes mellitus with relatively mild degrees of hepatic steatosis and neurodegeneration (96, 100-102).…”

“…This hypothesis is supported by experimental studies in which, the administration of intracerebroventricular streptozotocin, a glucosaminenitrosourea pro-diabetes compound, resulted in cognitive impairment with deficits in spatial learning and memory, brain insulin resistance and insulin deficiency, and AD-type neurodegeneration, but not diabetes mellitus (19,(96)(97)(98)(99). In contrast, parenteral administration of streptozotocin causes diabetes mellitus with relatively mild degrees of hepatic steatosis and neurodegeneration (96,(100)(101)(102). The alkylating properties of streptozotocin cause DNA damage, and uptake of streptozotocin by insulin producing cells, i.e.…”

Analysis of diabetes-related cerebellar changes in streptozotocin-induced diabetic rats

“…Results pointed to the glutamate pathway as a possible regulatory function in brain neural disturbances and neuronal degeneration in diabetes as a function of age (20).…”

Insulin Resistance, Cognitive Impairment and Neurodegeneration: Roles of Nitrosamine Exposure, Diet and Lifestyles

“…or i.v. administration of STZ also causes mild hepatic steatosis and neurodegeneration (Biju and Paulose 1998;Szkudelski 2001;Bolzan and Bianchi 2002;Koulmanda, Qipo et al 2003), but low dose ICV STZ treatment causes cognitive impairment with brain insulin resistance, brain insulin deficiency, and AD-type neurodegeneration, and not diabetes mellitus or hepatic steatosis (Biju and Paulose 1998;Nitta, Murai et al 2002;Weinstock and Shoham 2004;Lester-Coll, Rivera et al 2006 After all, human are not generally exposed to STZ. The probable answer was uncovered by the realization that STZ is a nitrosamine-related compound, and that over the past several decades, Western societies have been assaulted by continuous and growing exposures to environmental and food-related nitrosamines.…”

“…Even today, most cases of AD arise in the absence of type 2 diabetes, obesity, or metabolic syndrome, indicating that insulin/IGF resistance and deficiency can selectively involve the brain. Similarly, brain-only insulin and/or IGF resistance with cognitive impairment and AD-type neurodegeneration can be produced by intracerebroventricular (ICV) administration of small interfering (si)-RNA duplexes targeting the insulin or IGF receptors (see below), genetic depletion of insulin/IGF receptors, or ICV treatment with streptozotocin (STZ), which destroys insulin and IGF receptor bearing cells (Biju and Paulose 1998;Lannert and Hoyer 1998;Hoyer, Lee et al 2000;Nitta, Murai et al 2002;Weinstock and Shoham 2004;LesterColl, Rivera et al 2006;Grunblatt, Salkovic-Petrisic et al 2007;Labak, Foniok et al 2010;de la Monte, Tong et al 2011). These studies support a primary role for brain insulin/IGF resistance and deficiency as the cause of AD-type neurodegeneration.…”