The Effect of Hyperinsulinemia on Glucose Homeostasis During Moderate Exercise in Man

Abstract

Moderate exercise in man for 1 h results in a two- to threefold increase in glucose disappearance (Rd) and hepatic glucose production (Ra) so that euglycemia is maintained. The mechanism controlling the increase in Ra is not known, although circulating levels of insulin and glucagon have been suggested as important regulatory factors. To assess the importance of circulating insulin levels on exercise-induced glucose flux, we have examined the response to 60-min exercise on a bicycle ergometer at 60% maximal oxygen uptake (Vo2 max) in five normal male subjects on two occasions. A constant i.v. infusion of insulin (20 mU/kg/h) or saline was begun 60 min before exercise. Ra and Rd were measured by a non-steady-state constant [3-3H]glucose infusion technique. During the control (saline) study serum insulin (IRI) fell from 6.4 ± 1.8 (SEM) to 4.4 ± 1.4 mU/L (P < 0.05). During the insulin infusion IRI was maintained at 23.0 ± 0.8 mU/L with a modest drop in plasma glucose before exercise, 5.4 ± 0.2 to 4.0 ± 0.4 mmol/L. Hyperinsulinemia during exercise did not affect peak responses of either Ra (control 1.88 ±0.25 versus 2.00 ± 0.17 mmol/min, NS) or Rd (control 1.89 ± 0.26 versus 1.94 ± 0.18 mmol/min, NS) nor did it result in a significant fall in plasma glucose (control −0.2 ± 0.2 versus −0.2 ± 0.4 mmol/L). Moreover, plasma glucagon (IRG) had not changed significantly after 30-min exercise during insulin infusion when Ra had increased to 195% of the pre-exercise level. Plasma cortisol, norepinephrine, and growth hormone rose during exercise, but the elevation was not significantly greater during insulin infusion than in the control study. Thus, during moderate hyperinsulinemia in normal man, exercise does not cause a fall in plasma glucose and hepatic glucose output is undiminished. This study demonstrates that a decrease in IRI, elevation of IRG, or a change in IRI/IRG ratio are not important in initiating hepatic glucose output during exercise.