Renal Glucose Production During Insulin-Induced Hypoglycemia

Recent in vivo studies have rekindled interest in the role of the kidney 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 arteriovenous balance combined with a tracer technique. Ten days after the surgical placement of sampling catheters in the right and left renal veins 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 [6-³H]glucose. Renal blood flow was determined with a flowprobe. After baseline, six dogs received 2-h simultaneous infusions of peripheral insulin (4 mU · kg⁻¹ · min⁻¹) and left intrarenal [6,6-²H]dextrose (14 μmol · kg⁻¹ · min⁻¹) to achieve and maintain left renal normoglycemia during systemic hypoglycemia. Arterial glucose decreased from 5.3 ± 0.1 to 2.2 ± 0.1 mmol/1; insulin increased from 46 ± 5 to 1,050 ± 50 pmol/1; epinephrine increased from 130 ± 8 to 1,825 ± 50 pg/ml; norepinephrine increased from 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 increased from 16.6 ± 0.4 μmol · kg⁻¹ · min⁻¹ in the baseline to 24.2 ± 0.6 μmol · kg⁻¹ · min⁻¹ during hypoglycemia when endogenous glucose production was 10.2 ± 1.0 μmol · kg⁻¹ · min⁻¹ (P < 0.01). In the baseline, the liver accounted for 80% (13.3 ± 0.8 μmol · kg⁻¹ · min⁻¹) and each kidney contributed 10% (1.6 ± 0.2 μmol · kg⁻¹ · min⁻¹) to endogenous glucose production. During hypoglycemia, however, hepatic glucose production decreased to 4.0 ± 0.4 μmol · kg⁻¹ · min⁻¹, whereas right renal glucose production doubled to 3.2 ± 0.2 μmol · kg⁻¹ · min⁻¹ (P < 0.01). Left renal glucose production was 17 ± 2 μmol · kg⁻¹ · min⁻¹, 14 of which were derived from the exogenous infusion. These results indicate that glucose production by the kidney is stimulated by counterregulatory hormones and represents an important component of the body's defense against insulin-induced hypoglycemia.