Stimulatory effect of stevioside on peripheral mu opioid receptors in animals.
Stevioside is a dietary supplement widely used as a sweetener to prevent hyperglycemic disorders. However, the action mechanisms of this substance for glucose homeostasis remain obscure. In the present study, a dose-related plasma glucose reduction was observed in Wistar rats receiving intraperitoneally injections of stevioside. Similar to the regulation of glucose metabolism by the activation of mu opioid receptors, this action of stevioside was reversed by naloxonazine under the blockade of mu opioid receptors. We also found that stevioside increased glycogen synthesis in isolated hepatocytes, which was concentration-dependently blocked by naloxonazine. Stevioside did not modify the plasma beta-endorphin levels in Wistar rats but it directly increased the phosphorylation of mu opioid receptors in Chinese hamster ovary cells transfected with mu opioid receptors. Unlike morphine, chronic administration of stevioside did not induce the withdrawal signs in mice. Furthermore, stevioside by intraperitoneal injections did not influence the feeding behaviors of rats. By contrast, intracerebroventricular injections of stevioside increased the rats' food intake, which was also inhibited by pretreatment with naloxonazine. These results showed that it is difficult for stevioside to enter the brain. Stevioside has the ability to activate peripheral mu opioid receptors for lowering plasma glucose and to increase glycogen synthesis in liver. Thus, the stimulation of peripheral mu opioid receptors is responsible for the action of stevioside in the regulation of glucose homeostasis.
Yang
Po-Sheng
PS
Department of Surgery, Mackay Memorial Hospital, Taipei City, Taiwan, ROC.
Lee
Jie-Jen
JJ
Tsao
Chiung-Wen
CW
Wu
Hung-Tsung
HT
Cheng
Juei-Tang
JT
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D013549:Sweetening Agents / Q000494:pharmacology*
D001786:Blood Glucose; D045786:Diterpenes, Kaurane; D005960:Glucosides; D017450:Receptors, Opioid, mu; D013549:Sweetening Agents; C012043:stevioside; D006003:Glycogen