Decreased Glycaemia with Renal Failure in Diabetes Betides in Relation to the Change in Renal Glutamate Metabolism

Abstract

A reduction in renal gluconeogenesis appears to be one cause for the drop in blood glucose concentration (BGC) accompanying decreased renal function in diabetes. However, it remains unclear as to how this drop in BGC is related to the changes in reabsorption of amino acids (AAs) that accompany decreased renal function. We therefore investigated the relationship between the drop in BGC accompanying decreased renal function in diabetes patients and changes in the reabsorption rates of AAs. Subjects and methods: Using 100 diabetes patients and 100 non-diabetics as subjects, we measured their blood AAs concentration and urinary AAs excretion, and calculated the AAs’ reabsorption rate. We then examined the relationship between the latter and the estimated glomerular filtration rate (eGFR) and HbA1c. Results: In diabetics, blood glutamate concentration and reabsorption rate of glutamate were reduced. The blood glutamine concentration was increased; however, the reabsorption of glutamine was unchanged. The reabsorption rates of some AAs, including glutamate, showed a positive correlation with eGFR. However, a reduced reabsorption rate of glutamate was the only independent risk factor for reduced eGFR. Moreover, only the reabsorption rate of glutamate correlated positively with HbA1c. Conclusions: In diabetes, glutamate reabsorption shows a decline that parallels decreased renal function: this reduction is related to a drop in BGC. The reduction in the reabsorption of glutamate appears to influence renal gluconeogenesis by reducing the gluconeogenesis-adjusting factor (malate-aspartate shuttle), not by reducing gluconeogenic substrates. Further studies are therefore needed to examine the role glutamate plays in renal gluconeogenesis.