INSULIN REGULATION OF RENAL GLUCOSE-METABOLISM IN CONSCIOUS DOGS

Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glucose uptake. 10 d after surgical placement of sampling catheters in the left renal vein and femoral artery and a nonobstructive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [3-H-3]glucose and [2-C-14]glycerol. After baseline measurements, animals received a 2-h intrarenal infusion of either insulin (n = 6) or saline (n = 6). Left renal vein insulin concentration increased from 41+/-8 to 92+/-23 pmol/l(P < 0.05) in the insulin group, but there was no change in either arterial insulin, (similar to 50 pmol/l), glucose concentrations (similar to 5.4 mmol/l), or glucose appearance (similar to 18 mu mol . kg(-1) . min(-1)). Left renal glucose uptake increased from 3.1+/-0.4 to 5.4+/-1.4 mu mol . kg(-1) . min(-1) (P < 0.01) while left renal glucose production decreased from 2.6+/-0.9 to 0.7+/-0.5 mu mol . kg(-1) . min(-1) (P < 0.01) during insulin infusion. Penal gluconeogenesis from glycerol decreased from 0.23 +/- 0.06 to 0.17 +/- 0.04 mu mol . kg(-1) min(-1) (P < 0.05) during insulin infusion. These results indicate that renal glucose production and utilization account for similar to 30% of glucose turnover in postabsorptive dogs. Physiological hyperinsulinemia suppresses renal glucose production and stimulates renal glucose uptake by similar to 75%. We conclude that the kidney makes a major contribution to systemic glucose metabolism in the postabsorptive state.