Insulin regulation of renal glucose metabolism in humans

Eighteen healthy subjects had arterialized hand and renal veins catheterize d after an overnight fast. Systemic and renal glucose and glycerol kinetics were measured with [6,6-H-2(2)]glucose and [2-C-13]glycerol before and aft er 180-min peripheral infusions of insulin at 0.125 (LO) or 0.25 (HI) mU.kg (-1).min(-1) with variable [6,6-H-2(2)]dextrose or saline (control). Renal plasma flow was determined by plasma p-aminohippurate clearance. Arterial i nsulin increased from 37 +/- 8 to 53 +/- 5 (LO) and to 102 +/- 10 pM (HI, P < 0.01) but not in control(35 +/- 8 pM). Arterial glucose did not change a nd averaged 5.2 +/- 0.1 (control), 4.7 +/- 0.2 (LO), and 5.1 +/- 0.2 (HI) m u mol/ml; renal vein glucose decreased from 4.8 +/- 0.2 to 4.5 +/- 0.2 mu m ol/ml (LO) and from 5.3 +/- 0.2 to 4.9 +/- 0.1 mu mol/ml (HI) with insulin but not saline infusion (5.3 +/- 0.1 mu mol/ml). Endogenous glucose product ion decreased from 9.9 +/- 0.7 to 6.9 =/- 0.5 (LO) and to 5.7 +/- 0.5 (HI) mu mol.kg(-1).min(-1); renal glucose production decreased from 2.5 +/- 0.6 to 1.5 +/- 0.5 (LO) and to 1.2 +/- 0.6 (HI) mu mol.kg(-1).min(-1), whereas renal glucose utilization increased from 1.5 +/- 0.6 to 2.6 +/- 0.7 (LO) an d to 2.9 +/- 0.7 (HI) mu mol.kg(-1).min(-1) after insulin infusion tall P < 0.05 vs, baseline). Neither endogenous glucose production (10.0 +/- 0.4), renal glucose production (1.1 +/- 0.4), nor renal glucose utilization (0.8 +/- 0.4) changed in the control group. During insulin infusion, systemic gl uconeogenesis from glycerol decreased from 0.67 +/- 0.05 to 0.18 +/- 0.02 ( LO) and from 0.60 +/- 0.04 to 0.20 +/- 0.02 (HI) mu mol.kg(-1).min(-1) (P < 0.01), and renal gluconeogenesis from glycerol decreased from 0.10 +/- 0.0 2 to 0.02 +/- 0.02 (LO) and from 0.15 +/- 0.03 to 0.09 +/- 0.03 (HI) mu mol .kg(-1).min(-1) (P < 0.05). In contrast, during saline infusion, systemic ( 0.66 +/- 0.03 vs. 0.82 +/- 0.05 mu mol.kg(-1).min(-1)) and renal gluconeoge nesis from glycerol (0.11 +/- 0.02 vs. 0.41 +/- 0.04 mu mol.kg(-1).min(-1)) increased (P ( 0.05 vs. baseline). We conclude that glucose production and utilization by the kidney are important insulin-responsive components of g lucose metabolism in humans.