Insulin treatment prevents diabetes-induced alterations in astrocyte glutamate uptake and GFAP content in rats at 4 and 8 weeks of diabetes duration

Abstract

Rat astrocyte function is changed by diabetes mellitus relative to the nondiabetic state and we believe that altered function contributes to the central nervous system symptoms manifested by individuals with diabetes. We report here a comparison of astrocyte glutamate uptake and GFAP expression in streptozotocin-induced type 1 diabetic rats and insulin treated diabetic rats at four and eight weeks following diabetes onset. In glial plasmalemmal vesicle (GPV) preparations from treated rats, insulin prevented the increase observed in untreated, diabetic rats of both sodium-dependent and sodiumindependent glutamate uptake. We determined by immunoblotting and immunohistochemistry that insulin treatment prevented the decrease of GFAP expression detected in the cerebral cortex, hippocampus, and cerebellum of untreated, diabetic rats. These observations indicate that insulin effects on astrocyte function are significant in managing diabetes-induced central nervous system pathology.

Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem

“…Meanwhile, decreased astrocyte GFAP expression in type 1 diabetic rats was also found by other researchers with no additional harmful condition beyond diabetes (11,(18)(19)(20)(21)(22). On the other hand, insulin treatment has shown to prevent diabetes-induced decreases in astrocytic GFAP content (11) Although astrocytes were not individually counted in our study, the decrease in GFAP content seen in diabetic rats apparently reflected a decrease in GFAP expression rather than a decrease in the number of astrocytes.…”

“…This observation is similar to that of Coleman and cols. (11), and differs from Lechuga-Sancho and cols. (21), who reported a decrease in rat hypothalamic astrocyte numbers after 6 weeks of diabetes onset.…”

“…It is recognized that diabetes exacerbates astrocytic (7,8) and neuronal (9,10) damage induced by ischemia and reperfusion. On the other hand, insulin treatment prevents diabetes-induced alterations in astrocyte glutamate uptake and reverts the decreased GFAP expression in rats at 4 and 8 weeks of diabetes duration (11). Glial modifications were clearly pointed out in some studies (12,13) using streptozotocin-diabetic rats after the injection of EB, with marked delay on macrophagic scavenging activity of myelin debris, on oligodendrocyte and Schwann cell remyelination (12), as well as on blood-brain barrier repair (13), although astrocytic response was not properly investigated and compared between diabetic and non-diabetic animals.…”

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

“…It is recognized that diabetes exacerbated astrocytic (8,9) and neuronal (10,11) damage induced by ischemia and reperfusion. On the other hand, insulin treatment prevented diabetes-induced alterations in astrocyte glutamate uptake and reverted the decreased GFAP expression in rats at 4 and 8 weeks of diabetes duration (12). Glial modifications were clearly pointed in some studies using streptozotocin-diabetic rats after the injection of EB (13)(14)(15), with marked delay on macrophagic scavenging activity of myelin debris, on oligodendrocyte and Schwann cell remyelination (13), on blood-brain barrier repair (14) as well as on glial fibrillary acidic protein (GFAP) expression in reactive astrocytes at the periphery of the injury site (15).…”

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

“…Additionally, Acs are essential in fluid balance, glycogen storage for the energy supply (glucose-lactate) for neurons, regulation of glutamate reuptake, provision of antioxidant production via glutathione (GSH), protection of neurons from excessive ROS resulting in neurodegeneration, gliosis as a response-to-injury mechanism, and maintaining neuronal plasticity [31,32,33]. …”