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Citations to this article

Glucose transport in human skeletal muscle cells in culture. Stimulation by insulin and metformin.
V Sarabia, … , L A Leiter, A Klip
V Sarabia, … , L A Leiter, A Klip
Published October 1, 1992
Citation Information: J Clin Invest. 1992;90(4):1386-1395. https://doi.org/10.1172/JCI116005.
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Glucose transport in human skeletal muscle cells in culture. Stimulation by insulin and metformin.

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Abstract

Primary human muscle cell cultures were established and the regulation of glucose transport was investigated. Primary cultures were allowed to proceed to the stage of myotubes through fusion of myoblasts or were used for clonal selection based on fusion potential. In clonally selected cultures, hexose (2-deoxy-glucose) uptake into myotubes was linear within the time of study and inhibitable by cytochalasin B (IC50 = 400 nM). Cytochalasin B photolabeled a protein(s) of 45,000-50,000 D in a D-glucose-protectable manner, suggesting identity with the glucose transporters. In the myotube stage, the cells expressed both the GLUT1 and GLUT4 glucose transporter protein isoforms at an average molar ratio of 7:1. Preincubation in media of increasing glucose concentrations (range 5-25 mM) progressively decreased the rate of 2-deoxyglucose uptake. Insulin elevated 2-deoxyglucose uptake in a dose-dependent manner, with half maximal stimulation achieved at 3.5 nM. Insulin also stimulated the transport of the nonmetabolizable hexose 3-O-methylglucose, as well as the activity of glycogen synthase, responsible for nonoxidative glucose metabolism. The oral antihyperglycemic drug metformin stimulated the cytochalasin B-sensitive component of both 2-deoxyglucose and 3-O-methylglucose uptake. Maximal stimulation was observed at 8 h of exposure to 50 microM metformin, and this effect was not prevented by incubation with the protein-synthesis inhibitor cycloheximide. The relative effect of metformin was higher in cells incubated in 25 mM glucose than in 5 mM glucose, consistent with its selective action in hyperglycemic conditions in vivo. Metformin (50 microM for 24 h) was more effective than insulin (1 microM for 1 h) in stimulating hexose uptake and the hormone was effective on top of the stimulation caused by the biguanide, suggesting independent mechanisms of action.

Authors

V Sarabia, L Lam, E Burdett, L A Leiter, A Klip

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Metformin: A Review of its Pharmacological Properties and Therapeutic Use in Non-Insulin-Dependent Diabetes Mellitus
CJ Dunn, DH Peters
Drugs 1995
Importance of the intestine as a site of metformin-stimulated glucose utilization
CJ Bailey, KJ Mynett, T Page
British Journal of Pharmacology 1994
Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine
WC Stanley, JL Hall, KR Smith, GD Cartee, TA Hacker, JA Wisneski
Metabolism 1994
Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes
XY Yang, Z Fekete, J Gardner, J Benevenia, A Aviv
Hypertension 1994
DEMONSTRATION OF DEFECTIVE GLUCOSE UPTAKE AND STORAGE IN ERYTHROCYTES FROM NON-INSULIN DEPENDENT DIABETIC PATIENTS AND EFFECTS OF METFORMIN
RG Yoa, JR Rapin, NF Wiernsperger, A Martinand, I Belleville
Clinical and Experimental Pharmacology and Physiology 1993
Metformin—An update
CJ Bailey
General Pharmacology: The Vascular System 1993
Hormonal regulation of glucose transporters in muscle cells in culture
R Sargeant, Y Mitsumoto, V Sarabia, G Shillabeer, A Klip
Journal of Endocrinological Investigation 1993

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