SENSITIVITY OF EXERCISE-INDUCED INCREASE IN HEPATIC GLUCOSE-PRODUCTION TO GLUCOSE SUPPLY-AND-DEMAND

It was hypothesized that the exercise-induced changes in glucoregulato ry hormones and glucose production (R(a)) occur as a result of a small deficit in glucose availability. To test this, 18-h fasted dogs perfo rmed 150 min of treadmill exercise with either the liver as the sole s ource of glucose (controls, n = 5) or with glucose infused from 0 to 5 0 min (period 1) and from 100 to 150 min (period 3) at rates designed to track the glucose utilization (R(d)) response (ExoGlc, n = 5). The liver alone supplied glucose from 50 to 100 min (period 2). Isotopic a nd arteriovenous methods were used to assess R(a), R(d), and gluconeog enesis (GNG). Variable [H-3]glucose infusion and frequent sampling wer e used to facilitate R(a) measurements. Arterial glucose declined by - 3.1 +/- 1.4, -4.3 +/- 2.9, and -6.4 +/- 3.7 mg/dl in periods 1-3 in co ntrols (changes are mean values during each of the 50-min periods; P < 0.05). In ExoGlc, arterial glucose did not deviate from basal in peri ods 1 (+ 0.1 +/- 1.8 mg/dl) and 3 (+ 1.5 +/- 4.5 mg/dl) but fell from basal (P < 0.05) by the same amount as controls in period 2 (-5.7 +/- 2.1 mg/dl). Matching the R(d) response with exogenous glucose led to i ncreases in arterial and portal vein plasma insulin levels (P < 0.05) but did not affect glucagon, norepinephrine, epinephrine, and cortisol levels. R(a) was elevated by 3.1 +/- 0.5, 4.0 +/- 1.1, and 4.7 +/- 1. 1 mg.kg(-1).min(-1) in periods 1-3 in controls (P < 0.05). In ExoGlc, R(a) rose by 0.0 +/- 0.4, 4.1 +/- 1.4 (P < 0.05), and 0.4 +/- 0.7 mg.k g(-1).min(-1), respectively, in periods 1-3. The rise in R(a) was redu ced in periods 1 and 3 of ExoGlc compared with controls (P < 0.02). GN G rose to similar to 250% basal in controls and did not respond with a ny significant difference in ExoGlc. In summary, the exercise-induced increases in counterregulatory hormones and GNG are present even when a deficit in glucose supply is eliminated by an exogenous glucose infu sion. In contrast, the fall in insulin and the rise in hepatic glycoge nolysis are greatly attenuated. The regulatory components affected by exogenous glucose predominate at the liver as deviations in plasma glu cose of similar to 4% correspond to similar to 60% changes in R(a). In conclusion, the high sensitivity of the pancreatic beta-cell and live r to small deviations in glucose availability created by an exogenous glucose infusion supports the hypothesis that the exercise-induced ris e in R(a) is controlled, to a large extent, by a feedback signal propo rtional to the ratio of glucose supply and muscle glucose demand.