title: Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β-endorphin in type I-like diabetic rats.
abstract: Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycaemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β-endorphin-like immunoreactivity (BER) using enzyme-linked immunosorbent assay (ELISA). Diosmin also increased BER dose-dependently in the same manner. Repeated treatment of STZ-diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β-endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ-diabetic rats.
authors.affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan.|Chief Secretary 's Office, Chiayi Hospital, Ministry of Health and Welfare, Chiayi, Taiwan.
authors.forename: Mang Hung
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan.|Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan, Taiwan.
authors.forename: Juei Tang
authors.identifier: http://orcid.org/0000-0002-4522-584X
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Ming Chang
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002957:Citrus; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004145:Diosmin / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001615:beta-Endorphin / Q000097:blood*
chemical_list: D001786:Blood Glucose; D005419:Flavonoids; D007004:Hypoglycemic Agents; D001615:beta-Endorphin; D004145:Diosmin
keywords: STZ-diabetic rats; diosmin; opioid receptor; β-endorphin