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The biochemical mechanisms by which diabetes modulates cognitive function are not well established. Here, we determined the effects of streptozotocin (STZ) administration on the binding properties of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors in rats, using quantitative autoradiographic analysis of (3)H-AMPA and [(3)H]glutamate binding on brain tissue sections. The STZ injection (70 mg/kg intraperitoneally) produced a reduction of (3)H-AMPA binding in various brain regions, an effect that is due to a decrease in receptor affinity. The STZ-induced reduction of (3)H-AMPA binding varied in different brain structures, being more pronounced in the striatum, cerebral cortex, and hippocampus and almost absent in the cerebellum. Western blots performed on hippocampal membranes revealed that the decrease in (3)H-AMPA binding is possibly associated with changes in immunologic properties for one glutamate receptor subunit (GluR1). Finally, the effect of STZ-induced diabetes appeared to be specific to the AMPA subtype of glutamate receptors, as the same treatment did not modify [(3)H]glutamate binding to NMDA receptors. These changes in AMPA receptor properties may have important implications for understanding the biochemical mechanisms underlying cognitive impairment in diabetes.

The purpose of this study was to investigate the effects of recombinant human erythropoietin (rHuEPO) administration on energy metabolism during exercise. Specifically, the contribution of anaerobic (glycogen) metabolism during exercise was evaluated. Sprague-Dawley rats were randomly assigned to an experimental [rHuEPO] (600 U x kg(-1) of Eprex, every 3 days) or control (equivalent volume of saline) group. After 15 days of treatment, animals from both groups were randomly subjected to either a 30-minute exercise (swimming with 5% body weight added) or resting period. They were sacrificed at the end of the exercise period. Their liver and muscles were quickly removed and frozen in liquid nitrogen. Blood was also sampled. rHuEPO administration resulted in a significant (P < 0.05) increase of hematocrit (from 42 +/- 2 to 54 +/- 7 L/L). In the rHuEPO group, both muscle glycogen and free fatty acids were higher whereas lactate was lower at the conclusion of the exercise period (P < 0.05). These results suggest that energy substrate utilization during exercise is affected by enhanced oxygen availability. Finally, a lower overall contribution to energy production from anaerobic metabolism during exercise followed rHuEPO administration.

The binding properties of glucagon receptors were determined in plasma membranes isolated from liver of untrained (n = 6) and swimming endurance-trained Sprague-Dawley male rats (n = 7; 3 h/day, 5 days/wk, for 8 wk). Plasma membranes were purified from liver by aqueous two-phase affinity partitioning, and saturation kinetics were obtained by incubation of plasma membranes (10 microg of proteins/150 microl) with (125)I-labeled glucagon at concentrations ranging from 0.15 to 3.0 nM for 30 min at 30 degrees C. Saturating curve analysis indicated no difference in the affinity of glucagon receptors (0.57 +/- 0.06 and 0.77 +/- 0.09 nM in untrained and trained groups, respectively) but a significant higher glucagon receptor density in liver from untrained vs. trained rats (3.09 +/- 0.12 vs. 4.28 +/- 0.19 pmol/mg proteins). These results suggest that the reported increase in liver glucagon sensitivity in endurance-trained subjects (Drouin R, Lavoie C, Bourque J, Ducros F, Poisson D, and Chiasson J-L. Am J Physiol Endocrinol Metab 274: E23-E28, 1998) could be partly due to an increased glucagon receptor density in response to training.