Salacia oblonga extract increases glucose transporter 4-mediated glucose uptake in L6 rat myotubes: role of mangiferin.
OBJECTIVE
To evaluate if the antidiabetic properties of Salacia oblonga extract are mediated not only by inhibiting intestinal alpha-glycosidases but also by enhancing glucose transport in muscle and adipose cells.


METHODS
S. oblonga extract effects on 2-deoxy-D-glucose uptake were assayed in muscle L6-myotubes and 3T3-adipocytes. In L6-myotubes, the amount and translocation of glucose transporters were assayed. A fractionation of the extract was carried out to identify the active compounds. Furthermore, we analyzed the phosphorylation status of key components of signaling pathways that are involved in the molecular mechanisms regulating glucose uptake.


RESULTS
S. oblonga extract increased 2-deoxy-D-glucose uptake by 50% in L6-myotubes and 3T3-adipocytes. In L6-myotubes, the extract increased up to a 100% the GLUT4 content, activating GLUT4 promoter transcription and its translocation to the plasma membrane. Mangiferin was identified as the bioactive compound. Furthermore, mangiferin effects were concomitant with the phosphorylation of 5'-AMP-activated protein kinase without the activation of PKB/Akt. The effect of mangiferin on 2-deoxy-D-glucose uptake was blocked by GW9662, an irreversible PPAR-gamma antagonist.


CONCLUSIONS
S. oblonga extract and mangiferin may exert their antidiabetic effect by increasing GLUT4 expression and translocation in muscle cells. These effects are probably mediated through two independent pathways that are related to 5'-AMP-activated protein kinase and PPAR-gamma.
Girón
María Dolores
MD
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja sn, E-18071 Granada, Spain.
Sevillano
Natalia
N
Salto
Rafael
R
Haidour
Ali
A
Manzano
Manuel
M
Jiménez
M L
ML
Rueda
Ricardo
R
López-Pedrosa
José M
JM
D016475:3T3 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D000077154:Rosiglitazone; D049918:Salacia / Q000737:chemistry*; D045162:Thiazolidinediones / Q000494:pharmacology; D044004:Xanthones / Q000032:analysis / Q000494:pharmacology*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D010936:Plant Extracts; D045162:Thiazolidinediones; D044004:Xanthones; D000077154:Rosiglitazone; C013592:mangiferin; D003847:Deoxyglucose; D055372:AMP-Activated Protein Kinases