Effects of fluctuating glucose concentrations on oxidative metabolism of glucose in cultured neurons and astroglia

Abstract

The objective of the present study was to evaluate the effects of hyperglycemia on glucose metabolism of brain cells. Not only a sustained hyperglycemic state, but also a fluctuating plasma glucose concentration has been implicated in the pathogenesis of diabetic angiopathy. Acutely increasing plasma glucose levels have not been reported to alter glucose utilization of the brain as a whole. In the present study, we examined the effects of chronic (3 weeks) or short-term (24-hour) exposure to a high glucose concentration on the oxidative metabolism of neurons and astroglia. Cells were prepared from Sprague-Dawley rats and cultured in the presence of a high (22 mM) or low (5 mM) concentration of glucose. The high or low glucose media did not alter either the rates of [14C]deoxyglucose phosphorylation (an indicator of total glucose utilization) or [14C]lactate and [14C]pyruvate oxidation (indicators of oxidative glucose metabolism) in neurons. In contrast, chronic or short-term exposure to a high glucose concentration resulted in significant decreases in oxidation of [14C]acetate, an astrocyte-specific reporter molecule, or [14C]lactate and [14C]pyruvate oxidation in the astroglia. Thus, either chronic or short-term increases in the glucose concentration suppressed oxidative metabolism only in astroglia, indicating neuro-protective roles against hyperglycemic brain cell injury in diabetes mellitus. These different responses of neurons and astroglia may also shed new light on brain energy metabolism in diabetic patients with either chronic high or fluctuating plasma glucose concentrations.