RENAL GLUCOSE-PRODUCTION DURING INSULIN-INDUCED HYPOGLYCEMIA

Recent in vivo studies have rekindled interest in the role of the kidn ey in glucose metabolism. We therefore undertook the present study to evaluate the contribution of the kidney to systemic glucose production and utilization rates during insulin-induced hypoglycemia using arter iovenous balance combined with a tracer technique. Ten days after the surgical placement of sampling catheters in the right and left renal v eins and femoral artery and of an infusion catheter in the left renal artery of dogs, systemic and renal glucose kinetics were measured with the peripheral infusion of [6-H-3]glucose. Renal blood flow was deter mined with a flowprobe. After baseline, six dogs received 2-h simultan eous infusions of peripheral insulin (4 mU . kg(-1) . min(-1)) and lef t intrarenal [6,6-H-2]dextrose (14 mu mol . kg(-1) min(-1)) to achieve and maintain left renal normoglycemia during systemic hypoglycemia. A rterial glucose decreased from 5.3 +/- 0.1 to 2.2 +/- 0.1 mmol/l; insu lin increased from 46 +/- 5 to 1,050 +/- 50 pmol/l; epinephrine increa sed from 130 +/- 8 to 1,825 +/- 50 pg/ml; norepinephrine increased fro m 129 +/- 6 to 387 +/- 15 pg/ml; and glucagon increased from 52 +/- 2 to 156 +/- 12 pg/ml (all P < 0.01). Systemic glucose appearance increa sed from 16.6 +/- 0.4 mu mol . kg(-1) . min(-1) in the baseline to 24. 2 +/- 0.6 mu mol . kg(-1) . min(-1) during hypoglycemia when endogenou s glucose production was 10.2 +/- 1.0 mu mol . kg(-1) . min(-1) (P < 0 .01). In the baseline, the liver accounted for 80% (13.3 +/- 0.8 mu mo l . k(-1) . min(-1)) and each kidney contributed 10% (1.6 +/- 0.2 mu m ol . kg(-1) . min(-1)) to endogenous glucose production, During hypogl ycemia, however, hepatic glucose production decreased to 4.0 +/- 0.4 m u mol . kg(-1) . min(-1), whereas right renal glucose production doubl ed to 3.2 +/- 0.2 mu mol . kg(-1) . min(-1) (P < 0.01). Left renal glu cose production was 17 +/- 2 mu mol . kg(-1) . min(-1), 14 of which we re derived from the exogenous infusion. These results indicate that gl ucose production by the kidney is stimulated by counterregulatory horm ones and represents an important component of the body's defense again st insulin-induced hypoglycemia.