Suppression of Endogenous Glucose Production by Mild Hyperinsulinemia During Exercise Is Determined Predominantly by Portal Venous Insulin

Suppression of Endogenous Glucose Production by Mild Hyperinsulinemia During Exercise Is Determined Predominantly by Portal Venous Insulin Raul C. Camacho 1 , R. Richard Pencek 1 , D. Brooks Lacy 2 , Freyja D. James 1 and David H. Wasserman 1 1 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 2 Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee Address correspondence and reprint requests to Raul Camacho, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615. E-mail: raul.camacho{at}vanderbilt.edu Abstract Hyperinsulinemia during exercise in people with diabetes requiring exogenous insulin is a major clinical problem. The aim of this study was to assess the significance of portal vein versus arterial insulin to hepatic effects of hyperinsulinemia during exercise. Dogs had sampling (artery, portal vein, and hepatic vein) and infusion (vena cava and portal vein) catheters and flow probes (hepatic artery and portal vein) implanted >16 days before a study. Protocols consisted of equilibration (−130 to −30 min), basal (−30 to 0 min), and treadmill exercise (0–150 min) periods. Somatostatin was infused and glucagon and insulin were replaced in the portal vein to achieve basal arterial and portal vein levels at rest and simulated levels during the first 60 min of exercise. From 60 to 150 min of exercise, the simulated insulin infusion was sustained (C; n = 7), modified to selectively create a physiologic increment in arterial insulin (Pe; n = 7), or altered to increase arterial insulin as in Pe but with a concomitant increase in portal insulin (PePo; n = 7). Euglycemic clamps were performed in all studies. Portal and arterial insulin were 15 ± 2 and 4 ± 1 μU/ml (mean ± SE of all groups), respectively, at t = 60 min in all groups. Insulin levels were unchanged for the remainder of the exercise period in C. Arterial insulin was increased from 3 ± 1 to 14 ± 2 μU/ml, whereas portal insulin did not change in Pe after t = 60 min. Arterial insulin was increased from 3 ± 1 to 15 ± 2 μU/ml, and portal insulin was increased from 16 ± 3 to 33 ± 3 μU/ml in PePo after t = 60 min. Endogenous glucose production ( R a ) rose similarly from basal during the first 60 min of exercise in all groups (mean ± SE of all groups was from 2.2 ± 0.1 to 6.8 ± 0.5 mg · kg −1 · min −1 ). The increase in R a was sustaine