Influence of glycogen storage on vascular smooth muscle metabolism

Abstract

The role of glycogen as an oxidative substrate for vascular smooth muscle (VSM) remains controversial. To elucidate the importance of glycogen as an oxidative substrate and the influence of glycogen flux on VSM substrate selection, we systematically altered glycogen levels and measured metabolism of glucose, acetate, and glycogen. Hog carotid arteries with glycogen contents ranging from 1 to 11 micromol/g were isometrically contracted in physiological salt solution containing 5 mM [1-(13)C]glucose and 1 mM [1, 2-(13)C]acetate at 37 degrees C for 6 h. [1-(13)C]glucose, [1, 2-(13)C]acetate, and glycogen oxidation were simultaneously measured with the use of a (13)C-labeled isotopomer analysis of glutamate. Although oxidation of glycogen increased with the glycogen content of the tissue, glycogen oxidation contributed only approximately 10% of the substrate oxidized by VSM. Whereas [1-(13)C]glucose flux, [3-(13)C]lactate production from [1-(13)C]glucose, and [1, 2-(13)C]acetate oxidation were not regulated by glycogen content, [1-(13)C]glucose oxidation was significantly affected by the glycogen content of VSM. However, [1-(13)C]glucose remained the primary ( approximately 40-50%) contributor to substrate oxidation. Therefore, we conclude that glucose is the predominate substrate oxidized by VSM, and glycogen oxidation contributes minimally to substrate oxidation.

Oleate Oxidation and Mitochondrial Substrate Selection in Vascular Smooth Muscle

“…Studies of VSM oxidative metabolism have demonstrated the importance of glucose as an oxidative substrate [1, 2]. In these experiments, the short-chain fatty acid acetate (1 m M ) was used to represent total plasma fatty acids.…”

“…In these experiments, the short-chain fatty acid acetate (1 m M ) was used to represent total plasma fatty acids. In the presence of 5 m M glucose and with glycogen contents spanning the range reported in vivo for VSM (1–15 µmol/g), acetate comprises 30–50% of the substrates oxidized by VSM [1, 2]. However, this is probably an overestimate of the contribution of long-chain fatty acids to VSM oxidative metabolism, because short-chain fatty acids are oxidized to a greater extent than long-chain fatty acids [3].…”

“…However, a novel technique, 13 C-isotopomer analysis of glutamate, can directly measure the oxidation of three classes of substrates simultaneously, as assessed by the incorporation of 13 C-labeled carbons from the substrates into the citric acid cycle intermediates. This technique has been used previously to examine VSM substrate oxidation [1, 2]. The purpose of this study is to use 13 C-isotopomer analysis of glutamate to examine the oxidation of oleic acid, as a representative long-chain fatty acid, to determine the extent of VSM long-chain fatty acid oxidation relative to the oxidation of other exogenous and endogenous substrates.…”

The Role of Hypotheses in Current Research, Illustrated by Hypotheses on the Possible Role of Astrocytes in Energy Metabolism and Cerebral Blood Flow: From Newton to Now

“…A segregation can be explained by cytosolic "channeling" of metabolites from one enzyme to the next in a pathway. Such a channeling is known in vascular smooth muscle, where lactate formed by glycolysis is segregated from that formed by glycogenolysis (Allen and Hardin, 2000;Lynch and Paul, 1983). The channeling may not be restricted to the individual astrocyte in which lactate was produced.…”

Mapping of ATP, Glucose, Glycogen, and Lactate Concentrations Within the Arterial Wall

“…Based on data from independent groups, it has previously been estimated that glycogen stores can maintain ATP production for 38 minutes in contracting pig carotid arteries. 32 However, in our setup, ATP levels were maintained for 3 hours under well-oxygenated conditions. This might be explained by the fact that the vessel segments were unstimulated in our experiments and could thus be expected to have a substantially lower energy demand than contracting arteries.…”