Although the kidney both takes up and produces glucose, its net contribution to overall glucose homoeostasis is negligible since these two processes approximately counterbalance each other. Glucose uptake primarily occurs in the distal medullary segments of the nephron where the glycolytic enzymes are present in high concentration. The major metabolic fates of the glucose which is taken up by this region of the kidney are oxidation to carbon dioxide and conversion to lactate. In contrast, gluconeogenesis primarily occurs in the proximal tubular portion of the renal cortex where free fatty acids represent the major metabolic fuel which supplies the energy requirements of the cell. However, in certain conditions, including metabolic acidosis, prolonged fasting, and poorly controlled diabetes mellitus, renal gluconeogenesis can be enhanced markedly and a net output of glucose by the kidney is readily observed.