Effects of Chronic Beta Receptor Stimulation on Glucose Metabolism

The acute administration of a beta receptor-stimulating agent profoundly affects insulin-mediated glucose metabolism; however, little is known about the impact of chronic beta receptor stimulation on glucose metabolism and insulin sensitivity. We therefore investigated the effect of the chronic administration of a beta-2-agonist, terbutaline sulfate (TS), on glucose metabolism in 7 healthy, normal-weight, male volunteers between the ages of 21 and 30 yr. Studies were performed using the euglycemic, hyperinsulinemic (1.0 mU/min · kg) clamp technique before and after the oral administration of 5 mg of TS three times a day for 1 and 2 wk. Basal endogenous glucose production (EGP) (2.54 ± 0.11 versus 2.64 ± 0.14 mg/min · kg) and basal glucose oxidation (1.87 ± 0.16 versus 2.0 ± 0.2 mg/ min · kg) were unchanged by the chronic administration of TS. However, insulin-stimulated total glucose metabolism increased by 29% (7.0 ± 0.47 versus 9.05 ± 0.67 mg/min · kg; P < 0.02). Insulin-stimulated, nonoxidative glucose disposal increased by 45% (3.62 ± 0.42 versus 5.26 ± 0.48 mg/min · kg; P < 0.01), while insulin-stimulated glucose oxidation did not change significantly (3.38 ± 0.15 versus 3.79 ± 0.22 mg/min · kg). EGP was completely suppressed under both conditions. Mean basal plasma insulin concentration (41 ± 9 versus 49 ± 15 pmol/L) and insulin clearance during the clamp procedure was unchanged (477 ± 45 versus 474 ± 37 ml/min · m²). We conclude that chronic beta receptor stimulation with TS improves insulin-stimulated glucose disposal in man, mostly by improving nonoxidative glucose disposal, i.e., “glucose storage.” Mechanisms explaining these findings have not yet been elucidated. We suggest that an adaptive response of the sympathetic nervous system plays a role in this phenomenon.