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Regulation of Net Hepatic Glycogenolysis and Gluconeogenesis during Exercise: Impact of Type 1 Diabetes

Departments of Internal Medicine (K.F.P., R.B.) and Diagnostic Radiology (T.B.P.), Yale University School of Medicine, New Haven, Connecticut 06520-8020

Address all correspondence and requests for reprints to: Dr. Kitt Falk Petersen, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, S263, P.O. Box 208020, New Haven, Connecticut 06520-8020.

The effects of type 1 diabetes on the contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production (GP) at rest and during moderate (MOD) and high (HI) intensity running were examined in healthy control (n = 6) and type 1 diabetic (n = 5) subjects matched for age, weight, and maximum aerobic capacity by combined noninvasive measurements of hepatic glycogen content using ¹³C nuclear magnetic resonance spectroscopy and determination of GP using [6,6-²H₂]glucose. In the control subjects, GP increased in proportion to the intensity of the exercise [at rest (REST), 14.3 ± 0.5; MOD, 18.1 ± 0.9; HI, 28.8 ± 1.3 µmol/(kg-min); P = 0.001, three-way comparison], and this was accounted for by an increase in the percent contribution of net hepatic glycogenolysis to GP (REST, 32 ± 1%; MOD, 49 ± 5%; HI, 57 ± 5%; P = 0.006). In the diabetic subjects, resting rates of GP were 60% higher than those in the control subjects (P < 0.0001) and increased in proportion to the workload. In contrast, the contributions of net hepatic glycogenolysis to GP were consistently lower than those in the control subjects (REST, 20 ± 6%; MOD, 32 ± 13%; HI, 32 ± 3%; P = 0.006 vs. control), and the exaggerated rates of GP could be entirely accounted for by increased rates of gluconeogenesis. In conclusion, 1) increases in GP in healthy control subjects with exercise intensity can be entirely attributed to increases in net hepatic glycogenolysis. 2) In contrast, moderately controlled type 1 diabetic subjects exhibit increased rates of GP both at rest and during exercise, which can be entirely accounted for by increased gluconeogenesis.

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