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Carrier-mediated fructose uptake significantly contributes to carbohydrate metabolism in human skeletal muscle.

ABSTRACT: To determine whether fructose can be utilized as a metabolic substrate for skeletal muscle in man, we investigated its incorporation into glycogen, its oxidation and lactate production in isolated human skeletal muscle. Rates of fructose oxidation and incorporation into glycogen increased in the presence of increasing fructose concentrations (0.1-1.0 mM). Lactate production increased 3-fold when extracellular fructose was increased from 0.1 to 0.5 mM. Cytochalasin B, a competitive inhibitor of hexose transport mediated by the GLUT1 and GLUT4 facilitative glucose transporters, completely inhibited insulin-stimulated glucose incorporation into glycogen and glucose oxidation (P < 0.01), but did not alter fructose incorporation into glycogen or fructose oxidation. Insulin (1000 mu-units/ml) increased glucose incorporation into glycogen 2.7-fold and glucose oxidation 2.3-fold, whereas no effect on fructose incorporation into glycogen or fructose oxidation was noted. A physiological concentration of glucose (5 mM) decreased the rate of 0.5 mM fructose incorporation into glycogen by 60% (P < 0.001), whereas fructose oxidation was not altered in the presence of 5 mM glucose. Irrespective of fructose concentration, the majority of fructose taken up underwent non-oxidative metabolism. Lactate production accounted for approx. 80% of the fructose metabolism in the basal state and approx. 70% in the insulin (1000 mu-units/ml)-stimulated state. In the presence of 5 mM glucose, physiological concentrations of fructose could account for approximately 10-30% of hexose (glucose + fructose) incorporation into glycogen under non-insulin-stimulated conditions. In conclusion, fructose appears to be transported into human skeletal muscle via a carrier-mediated system that does not involve GLUT4 or GLUT1. Furthermore, under physiological conditions, fructose can significantly contribute to carbohydrate metabolism in human skeletal muscle.

SUBMITTER: Zierath JR

PROVIDER: S-EPMC1136029 | biostudies-other | 1995 Oct

REPOSITORIES: biostudies-other

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Project description:The physiology of small mammalian hibernators shifts profoundly over a year, from summer homeothermy to winter heterothermy. Torpor-arousal cycles define high-amplitude tissue activity fluctuations in winter, particularly for skeletal muscle, which contributes to the energetically demanding rewarming process via shivering. To better understand the biochemistry underlying summer-winter and torpor-arousal transitions, we applied two-dimensional gel electrophoresis coupled with liquid chromatography/mass spectrometry/mas spectrometry to the soluble proteins from hindlimb muscle of 13-lined ground squirrels (Ictidomys tridecemlineatus) in two summer and six winter states. Two hundred sixteen protein spots differed by sampled state. Significantly, intrawinter protein adjustment was a minor component of the dataset despite large discrepancies in muscle activity level among winter states; rather, the bulk of differences (127/138 unequivocally identified proteins spots) occurred between summer and winter. We did not detect any proteomic signatures of skeletal muscle atrophy in this hibernator nor any differential seasonal regulation of protein metabolism. Instead, adjustments to metabolic substrate preferences dominated the detected proteomic differences. Pathways of carbohydrate metabolism (glycolysis and gluconeogenesis) were summer enriched, whereas the winter proteome was enriched for fatty acid β-oxidation. Nevertheless, our data suggest that some reliance on carbohydrate reserves is maintained during winter. Phosphoglucomutase (PGM1), which reversibly prepares glucose subunits for either glycolysis or glycogenesis, showed apparent winter state-specific phosphorylation. PGM1 was phosphorylated during rewarming and dephosphorylated by interbout arousal, implying that glucose supplements lipid fuels during rewarming. This, along with winter elevation of TCA cycle enzymes, suggests that hindlimb muscles are primed for rapid energy production and that carbohydrates are an important fuel for shivering thermogenesis.

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Carrier-mediated fructose uptake significantly contributes to carbohydrate metabolism in human skeletal muscle.

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