Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats

Abstract The influence of diabetes on brain glutamate (GLU) uptake was studied in insulinopenic (streptozotocin [STZ]) and insulin-resistant (diet-induced obesity [DIO]) rat models of diabetes. In the STZ study, adult male Sprague-Dawley rats were treated with STZ (65 mg/kg intravenously) or vehicle and studied 3 weeks later. The STZ rats had elevated plasma levels of glucose, ketone bodies, and branched-chain amino acids; brain uptake of GLU was very low in both STZ and control rats, examined under conditions of normal and greatly elevated (by intravenous infusion) plasma GLU concentrations. In the DIO study, rats ingested a palatable, high-energy diet for 2 weeks and were then divided into weight tertiles: rats in the heaviest tertile were designated DIO; rats in the lightest tertile, diet-resistant (DR); and rats in the intermediate tertile, controls. The DIO and DR rats continued to consume the high-energy diet for 4 more weeks, whereas the control rats were switched to standard rat chow. All rats were studied at 6 weeks (subgroups were examined under conditions of normal or elevated plasma GLU concentrations). The DIO rats ate more food and were heavier than the DR or control rats and had higher plasma leptin levels and insulin-glucose ratios. In all diet groups, the blood-brain barrier showed very low GLU penetration and was unaffected by plasma GLU concentration. Brain GLU uptake also did not differ among the diet groups. Together, the results indicate that the blood-brain barrier remains intact to the penetration of GLU in 2 models of diabetes under the conditions examined.