Regulation of net hepatic glycogenolysis and gluconeogenesis during exercise: impact of type 1 diabetes

Abstract

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 (13)C nuclear magnetic resonance spectroscopy and determination of GP using [6,6-(2)H(2)]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 micromol/(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.

Fig. 1

Plasma glucose concentrations at rest and during MOD (A) and HI (B) in control and diabetic subjects. To convert values to milligrams per deciliter, multiply by 0.0551.

Fig. 2

Plasma insulin concentrations at rest and during MOD (A) and HI (B) in control and diabetic subjects. To convert values to microunits per milliliter, divide by 6.

Fig. 3

Plasma glucagon concentrations at rest and during MOD (A) and HI (B) in control and diabetic subjects. To convert values to nanograms per liter, divide by 1.

Fig. 4

Rates of net hepatic glycogenolysis (millimoles per liter of liver per minute) at rest and during MOD and HI in control (□) and diabetic (■) subjects. Cx, Control; DM, type 1 diabetes mellitus.

Fig. 5

The contributions of net hepatic glycogenolysis and gluconeogenesis to rates of glucose production [μmol/(kg-min)] at rest and during MOD and HI in control (A) and diabetic (B) subjects.