ABNORMAL RENAL AND HEPATIC GLUCOSE-METABOLISM IN TYPE-2 DIABETES-MELLITUS

Release of glucose by liver and kidney are both increased in diabetic animals, Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The pre sent experiments were therefore undertaken to assess the relative cont ributions of hepatic and renal glucose release to the excessive glucos e release found in type 2 diabetes, Using a combination of isotopic an d balance techniques to determine total systemic glucose release and r enal glucose release in postabsorptive type 2 diabetic subjects and ag e-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release, Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 mu mol/min, P < 0.001), Hepatic glucose release was increased similar to 30% (P = 0 .03), but increments in hepatic and renal glucose release were compara ble (2.60+/-0.70 vs. 2.21+/-0.32, mu mol.kg(-1).min(-1), respectively, P = 0,26). Renal glucose uptake was markedly increased in diabetic su bjects (353 +/- 48 vs. 103 +/- 10 mu mol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92 +/- 50 mu mol/ min) versus a net output in the nondiabetic subjects (21 +/- 14 mu mol /min, P = 0.043). Renal glucose uptake was inversely correlated with r enal FFA uptake (r = -0.51, P < 0.01), which was reduced by similar to 60% in diabetic subjects (10.9+/-2.7 vs. 27.0+/-3.3 mu mol/min, P < 0 .002), We conclude that in type 2 diabetes, both liver and kidney cont ribute to glucose overproduction and that renal glucose uptake is mark edly increased. The latter may suppress renal FFA uptake via a glucose -fatty acid cycle and explain the accumulation of glycogen commonly fo und in the diabetic kidney.