Insulin regulation of renal glucose metabolism in humans.

Eighteen healthy subjects had arterialized hand and renal veins catheterized after an overnight fast. Systemic and renal glucose and glycerol kinetics were measured with [6,6-2H2]glucose and [2-13C]glycerol before and after 180-min peripheral infusions of insulin at 0.125 (LO) or 0.25 (HI) mU. kg-1. min-1 with variable [6, 6-2H2]dextrose or saline (control). Renal plasma flow was determined by plasma p-aminohippurate clearance. Arterial insulin 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 and averaged 5.2 +/- 0.1 (control), 4.7 +/- 0.2 (LO), and 5.1 +/- 0. 2 (HI) micromol/ml; renal vein glucose decreased from 4.8 +/- 0.2 to 4.5 +/- 0.2 micromol/ml (LO) and from 5.3 +/- 0.2 to 4.9 +/- 0.1 micromol/ml (HI) with insulin but not saline infusion (5.3 +/- 0.1 micromol/ml). Endogenous glucose production decreased from 9.9 +/- 0. 7 to 6.9 +/- 0.5 (LO) and to 5.7 +/- 0.5 (HI) micromol. 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) micromol. kg-1. min-1, whereas renal glucose utilization increased from 1.5 +/- 0.6 to 2.6 +/- 0.7 (LO) and to 2.9 +/- 0.7 (HI) micromol. kg-1. min-1 after insulin infusion (all 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 gluconeogenesis 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) micromol. kg-1. min-1 (P < 0.01), and renal gluconeogenesis from glycerol decreased from 0.10 +/- 0.02 to 0.02 +/- 0.02 (LO) and from 0.15 +/- 0.03 to 0.09 +/- 0.03 (HI) micromol. kg-1. min-1 (P < 0.05). In contrast, during saline infusion, systemic (0.66 +/- 0.03 vs. 0.82 +/- 0.05 micromol. kg-1. min-1) and renal gluconeogenesis from glycerol (0.11 +/- 0.02 vs. 0. 41 +/- 0.04 micromol. 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 glucose metabolism in humans.