Insulin-sensitizing activities of tanshinones, diterpene compounds of the root of Salvia miltiorrhiza Bunge.
In this study, the effects of the extract and four tanshinone compounds from the dried root of Salvia miltiorrhiza Bunge (Labiatae) on the tyrosine phosphorylation of the insulin receptor (IR) beta-subunit and the downstream signaling were examined in Chinese-hamster ovary cells expressing human insulin receptors (CHO/IR cells) as well as in 3T3-L1 adipocytes. In addition the translocation of the glucose transporter 4 was investigated in 3T3-L1 adipocytes. Total extract of Danshen (1-10 microg/ml) and the four tanshinones (10 microM) did not show any activity, but the total extract and the tanshinone I, IIA and 15, 16-dihydrotanshinone I except cryptotanshinone enhanced the activity of insulin (1 nM) on the tyrosine phosphorylation of the IR as well as the activation of the downstream kinases Akt, ERK1/2, and GSK3beta. In the adipocytes the same IR-downstream signaling and the translocation of glucose transporter 4 were demonstrated by the three tanshinones in the presence of insulin. These insulin-sensitizing activities of tanshinones may be useful for developing a new class of specific IR activators as anti-diabetic agents.
Jung
Seung Hee
SH
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
Seol
Hee Jung
HJ
Jeon
Su Jin
SJ
Son
Kun Ho
KH
Lee
Jong Ran
JR
D041721:3T3-L1 Cells; D045784:Abietanes; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D051275:Glucose Transporter Type 4 / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000819:agonists*; D051379:Mice; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D011972:Receptor, Insulin / Q000819:agonists*; D027561:Salvia miltiorrhiza; D014443:Tyrosine / Q000378:metabolism
D045784:Abietanes; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D010616:Phenanthrenes; D010936:Plant Extracts; C021751:tanshinone; D014443:Tyrosine; D010770:Phosphotransferases; D011972:Receptor, Insulin