Mediation of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in streptozotocin-induced diabetic rats.
We investigated the plasma glucose-lowering mechanism(s) of Rh2, a ginsenoside derived from Panax ginseng, in rats with streptozotocin-induced diabetes (STZ-diabetic rats). After intravenous injection over 120 min into fasting STZ-diabetic rats, Rh2 decreased plasma glucose in a dose-dependent manner. In parallel to the lowering of plasma glucose, an increase of plasma beta-endorphin-like immunoreactivity was observed. In addition, naloxone and naloxonazine at doses sufficient to block opioid mu-receptors inhibited the plasma glucose-lowering action of Rh2 in genetically wild-type, diabetic mice. In contrast, Rh2 failed to lower plasma glucose in opioid mu-receptor knockout diabetic mice. An increase in gene expression at both the mRNA and protein levels of glucose transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained from STZ-diabetic rats treated with Rh2 three times daily for one day; this increase in expression was absent when opioid mu-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in beta-endorphin secretion that activates opioid mu-receptors thereby resulting in an increased expression of GLUT 4.
Lai
Dar-Ming
DM
Neurosurgical Division, Department of Surgery, National Taiwan University Hospital, Taipei City, Taiwan, R.O.C.
Tu
Yong-Kwang
YK
Liu
I-Min
IM
Chen
Pei-Feng
PF
Cheng
Juei-Tang
JT
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D005894:Panax; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013311:Streptozocin; D001615:beta-Endorphin / Q000187:drug effects*
D001786:Blood Glucose; D036145:Ginsenosides; D051275:Glucose Transporter Type 4; D017450:Receptors, Opioid, mu; D013311:Streptozocin; D001615:beta-Endorphin; C055305:ginsenoside Rh2