DAR-MING LAIYONG-KWANG TULiu, I.-MinI.-MinLiuChen, Pei-FengPei-FengChenCheng, Juei-TangJuei-TangCheng2020-03-122020-03-1220060032-0943https://www.scopus.com/inward/record.uri?eid=2-s2.0-32644455714&doi=10.1055%2fs-2005-916177&partnerID=40&md5=6d4016755a59e6ca1139d4a77d44fefehttps://scholars.lib.ntu.edu.tw/handle/123456789/475997We 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 β-endorphin-like immunoreactivity was observed. In addition, naloxone and naloxonazine at doses sufficient to block opioid μ-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 μ-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 μ-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in β-endorphin secretion that activates opioid μ-receptors thereby resulting in an increased expression of GLUT 4. ? Georg Thieme Verlag KG Stuttgart.en[SDGs]SDG3beta endorphin; ginsenoside; ginsenoside Rh 2; glucose; glucose transporter 4; messenger RNA; mu opiate receptor; naloxonazine; naloxone; unclassified drug; animal experiment; animal model; animal tissue; article; controlled study; diabetes mellitus; dose response; drug mechanism; gene expression; ginseng; glucose blood level; immunoreactivity; knockout mouse; male; nonhuman; rat; receptor upregulation; soleus muscle; streptozocin diabetes; wild type; Animals; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Experimental; Ginsenosides; Glucose Transporter Type 4; Male; Mice; Panax; Phytotherapy; Rats; Rats, Wistar; Receptors, Opioid, mu; Streptozocin; Animalia; Panax ginsengjournal article10.1055/s-2005-916177164502892-s2.0-32644455714