Differential Regulation of Glucose and Glycogen Metabolism in Vascular Smooth Muscle by Exogenous Substrates

Abstract

The aim of this study was to determine whether the pathways of glycolysis and glycogenolysis can be independently modulated by the provision of acetate or pyruvate as exogenous substrates. Hog carotid artery segments were allowed to replete glycogen stores to over 6μmol/g of new13C-labeled glycogen by incubation at 37°C with 5 mm[1-13C]glucose for 6–16 h and then were isometrically contracted for 3 h with 80 mmKCl in the presence of 5 mm[2-13C]glucose and either 2 mmsodium acetate or 5 mmsodium pyruvate. Measurements were made of total lactate production, glucose utilization, glycogen utilization, isometric force, [2-13C]lactate and [3-13C]lactate production. Compared to experiments with glucose as the sole exogenous substrate, provision of pyruvate significantly decreased glucose utilization (by 28%) but insignificantly decreased glycogen utilization. In contrast, provision of acetate resulted in a statistically insignificant decrease in glucose utilization (by 23%) and an increase in glycogen utilization (by 20%). The fraction of [3-13C]pyruvate derived from glycogen that was converted to [3-13C]lactate was significantly decreased in the presence of acetate despite the enhanced glycogen utilization. Despite these alterations in cellular energy balance, isometric force generation and maintenance was similar for all experimental groups. This differential regulation of glycolysis and glycogenolysis may either reflect the compartmentation of these pathways or suggest a novel regulation of carbohydrate metabolismin vivo.