Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway.
Four cucurbitane glycosides, momordicosides Q, R, S, and T, and stereochemistry-established karaviloside XI, were isolated from the vegetable bitter melon (Momordica charantia). These compounds and their aglycones exhibited a number of biologic effects beneficial to diabetes and obesity. In both L6 myotubes and 3T3-L1 adipocytes, they stimulated GLUT4 translocation to the cell membrane--an essential step for inducible glucose entry into cells. This was associated with increased activity of AMP-activated protein kinase (AMPK), a key pathway mediating glucose uptake and fatty acid oxidation. Furthermore, momordicoside(s) enhanced fatty acid oxidation and glucose disposal during glucose tolerance tests in both insulin-sensitive and insulin-resistant mice. These findings indicate that cucurbitane triterpenoids, the characteristic constituents of M. charantia, may provide leads as a class of therapeutics for diabetes and obesity.
Tan
Min-Jia
MJ
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Ye
Ji-Ming
JM
Turner
Nigel
N
Hohnen-Behrens
Cordula
C
Ke
Chang-Qiang
CQ
Tang
Chun-Ping
CP
Chen
Tong
T
Weiss
Hans-Christoph
HC
Gesing
Ernst-Rudolf
ER
Rowland
Alex
A
James
David E
DE
Ye
Yang
Y
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D029777:Momordica charantia / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D013729:Terpenes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose