Regulation of splanchnic and renal substrate supply by insulin in humans

To determine the effects of peripheral insulin infusion on total, hepatic, and renal glucose production and on the percent contribution to glucose pro duction of gluconeogenesis versus glycogenolysis, 10 healthy subjects had a rterialized hand and hepatic vein catheterization after an overnight fast a nd the results were compared with data from 12 age- and weight-matched subj ects with renal vein catheterization during a 180-minute infusion of either insulin (0.25 mU/kg min) with dextrose, or saline. Endogenous, hepatic, an d renal glucose production was measured with [6,6-H-2(2)]glucose, regional lactate, alanine, and glycerol balance by arteriovenous difference; hepatic blood flow by indocyanine green clearance; and renal blood flow by p-amino hippurate clearance, before and every 30 minutes during each infusion perio d. Insulin increased from about 42 to 98 pmol/L and blood glucose remained constant in all studies (3.8 +/- 0.2 v 4.4 +/- 0.1 mu mol/ml, hepatic v ren al vein). In response to insulin infusion, endogenous, hepatic, and renal g lucose production decreased immediately (30 minutes) and reached a lower pl ateau value (10.8 +/- 0.8 v 6.4 +/- 0.7, 10.4 +/- 1.1 v 7.8 +/- 1.0, and 2. 8 +/- 0.6 v 1.5 +/- 0.6 mu mol/kg min, respectively) between 120 and 180 mi nutes (all P < .05). Net renal uptake of lactate (2.4 +/- 0.4 v 0.9 +/- 0.6 ) decreased earlier (30 minutes) and returned to baseline between 120 and 1 80 minutes (2.4 +/- 0.5 mu mol/kg min), whereas net splanchnic uptake of la ctate (5.7 +/- 0.7 v 0.7 +/- 0.6) and alanine (1.8 +/- 0.1 v 1.0 +/- 0.5 mu mol/kg min) decreased later (120 to 180 minutes). Net renal (0.3 +/- 0.1 v 0.1 +/- 0.1) and splanchnic (0.7 +/- 0.3 v 0.4 +/- 0.2 mu mol/kg min) glyc erol uptake decreased 90 to 180 minutes after insulin and increased (P < .0 5) with saline infusion (0.4 +/- 0.1 v 0.6 +/- 0.3 and 1.0 +/- 0.5 v 1.8 +/ - 0.4 mu mol/kg min, respectively). These data indicate that the rapid supp ression of endogenous glucose production by insulin reflects primarily a de crease in hepatic glucose release, most likely due to inhibition of net gly cogenolysis, combined with suppression of renal gluconeogenesis. Inhibition of hepatic gluconeogenesis presumably occurs later during hyperinsulinemia . We conclude that peripheral insulin, in addition to its inhibition of gly cogen degradation, regulates endogenous glucose production, in part, by mod ifying the splanchnic and renal substrate supply. Copyright (C) 2000 by W.B . Saunders Company.