Indinavir uncovers different contributions of GLUT4 and GLUT1 towards glucose uptake in muscle and fat cells and tissues.

Rudich, A. and Konrad, D. and Török, Dóra and Ben-Romano, R. and Huang, C. (2003) Indinavir uncovers different contributions of GLUT4 and GLUT1 towards glucose uptake in muscle and fat cells and tissues. DIABETOLOGIA, 46 (5). pp. 649-658. ISSN 0012-186X

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AIMS/HYPOTHESIS: Insulin-dependent glucose influx in skeletal muscle and adipocytes is believed to rely largely on GLUT4, but this has not been confirmed directly. We assessed the relative functional contribution of GLUT4 in experimental models of skeletal muscle and adipocytes using the HIV-1 protease inhibitor indinavir. METHODS: Indinavir (up to 100 micro mol/l) was added to the glucose transport solution after insulin stimulation of wild-type L6 muscle cells, L6 cells over-expressing either GLUT4myc or GLUT1myc, 3T3-L1 adipocytes, isolated mouse brown or white adipocytes, and isolated mouse muscle preparations. RESULTS: 100 micro mol/l indinavir inhibited 80% of both basal and insulin-stimulated 2-deoxyglucose uptake in L6GLUT4myc myotubes and myoblasts, but only 25% in L6GLUT1myc cells. Cell-surface density of glucose transporters was not affected. In isolated soleus and extensor digitorum longus muscles, primary white and brown adipocytes, insulin-stimulated glucose uptake was inhibited 70 to 80% by indinavir. The effect of indinavir on glucose uptake was variable in 3T3-L1 adipocytes, averaging 45% and 67% inhibition of basal and maximally insulin-stimulated glucose uptake, respectively. In this cell, fractional inhibition of glucose uptake by indinavir correlated positively with the fold-stimulation of glucose uptake by insulin, and was higher with sub-maximal insulin concentrations. The latter finding coincided with an increase only in GLUT4, but not GLUT1, in plasma membrane lawns. CONCLUSION/INTERPRETATION: Indinavir is a useful tool to assess different functional contributions of GLUT4 to glucose uptake in common models of skeletal muscle and adipocytes.

Item Type: Article
Uncontrolled Keywords: Recombinant Fusion Proteins/metabolism; Muscle, Skeletal/drug effects/*metabolism; *Muscle Proteins; Monosaccharide Transport Proteins/drug effects/genetics/*metabolism; MICE; Insulin/pharmacology; Indinavir/*pharmacology; Humans; HIV Protease Inhibitors/pharmacology; Glucose Transporter Type 4; Glucose Transporter Type 1; Glucose/*metabolism; Cell Membrane/metabolism; Biological Transport/drug effects; Animals; Adipose Tissue, Brown/drug effects/metabolism; Adipose Tissue/drug effects/metabolism; Adipocytes/drug effects/*metabolism; 3T3 Cells
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 31 Mar 2017 11:58
Last Modified: 31 Mar 2017 11:58

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