Dehydrotrametenolic acid induces preadipocyte differentiation and sensitizes animal models of noninsulin-dependent diabetes mellitus to insulin.
We recently discovered that the triterpene acid compound dehydrotrametenolic acid promotes adipocyte differentiation in vitro and acts as an insulin sensitizer in vivo. This natural product has been isolated from dried sclerotia of Poria cocos WOLF (Polyporaceae), a well-known traditional Chinese medicinal plant. We examined the effects of dehydrotrametenolic acid on plasma glucose concentration in obese hyperglycemic db/db mice. Dehydrotrametenolic acid can reduce hyperglycemia in mouse models of noninsulin-dependent diabetes mellitus (NIDDM) and act as an insulin sensitizer as indicated by the results of the glucose tolerance test. These terpenoids and thiazolidine type of antidiabetic agents such as Ciglitazone, although structurally unrelated, share many biological activities: both induce adipose conversion, activate peroxisome proliferator-activated receptor gamma (PPAR gamma) in vitro, and reduce hyperglycemia in animal models of NIDDM. Dehydrotrametenolic acid is a promising candidate for a new type of insulin-sensitizing drug. This finding is very important for the development of insulin sensitizers that are not of the thiazolidine type.
Sato
Mayumi
M
Department of Medicinal Pharmacology Research and Development, Tokyo Metropolitan Institute for Medical Science, Japan. sato@rinshoken.or.jp
Tai
Takaaki
T
Nunoura
Yoshiki
Y
Yajima
Yukiko
Y
Kawashima
Seiichi
S
Tanaka
Keiji
K
D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011124:Polyporaceae / Q000737:chemistry*; D011506:Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D014315:Triterpenes; C459482:dehydrotrametenolic acid