Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats
Summary 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 acti...
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| Veröffentlicht in: | Clinical and experimental pharmacology & physiology 2017-05, Vol.44 (5), p.549-555 |
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| creator | Hsu, Chia‐Chen Lin, Mang Hung Cheng, Juei Tang Wu, Ming Chang |
| description | Summary
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. |
| doi_str_mv | 10.1111/1440-1681.12739 |
| format | Article |
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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.</description><identifier>ISSN: 0305-1870</identifier><identifier>EISSN: 1440-1681</identifier><identifier>DOI: 10.1111/1440-1681.12739</identifier><identifier>PMID: 28218955</identifier><language>eng</language><publisher>Australia</publisher><subject>Animals ; beta-Endorphin - blood ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Citrus ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - drug therapy ; diosmin ; Diosmin - pharmacology ; Diosmin - therapeutic use ; Dose-Response Relationship, Drug ; Flavonoids - pharmacology ; Flavonoids - therapeutic use ; Hyperglycemia - blood ; Hyperglycemia - drug therapy ; Hypoglycemic Agents - pharmacology ; Hypoglycemic Agents - therapeutic use ; Male ; opioid receptor ; Rats ; Rats, Sprague-Dawley ; STZ‐diabetic rats ; β‐endorphin</subject><ispartof>Clinical and experimental pharmacology & physiology, 2017-05, Vol.44 (5), p.549-555</ispartof><rights>2017 John Wiley & Sons Australia, Ltd</rights><rights>2017 John Wiley & Sons Australia, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2589-df52b3caaebd1b258a6b8f249b0216668ebf9ae256fa133dd4f5e61816cc16cc3</citedby><cites>FETCH-LOGICAL-c2589-df52b3caaebd1b258a6b8f249b0216668ebf9ae256fa133dd4f5e61816cc16cc3</cites><orcidid>0000-0002-4522-584X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1440-1681.12739$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1440-1681.12739$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28218955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Chia‐Chen</creatorcontrib><creatorcontrib>Lin, Mang Hung</creatorcontrib><creatorcontrib>Cheng, Juei Tang</creatorcontrib><creatorcontrib>Wu, Ming Chang</creatorcontrib><title>Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats</title><title>Clinical and experimental pharmacology & physiology</title><addtitle>Clin Exp Pharmacol Physiol</addtitle><description>Summary
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.</description><subject>Animals</subject><subject>beta-Endorphin - blood</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Citrus</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - drug therapy</subject><subject>diosmin</subject><subject>Diosmin - pharmacology</subject><subject>Diosmin - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flavonoids - pharmacology</subject><subject>Flavonoids - therapeutic use</subject><subject>Hyperglycemia - blood</subject><subject>Hyperglycemia - drug therapy</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Male</subject><subject>opioid receptor</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>STZ‐diabetic rats</subject><subject>β‐endorphin</subject><issn>0305-1870</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv2yAYhlG1qs3SnnubOO5Qt2AbYh-jqNsqRWoP7Rlh-EjobMjA3pTbLr33t-yH7EfslxQ3aa5DQohXD--HHoQuKLmiaV3TsiQZ5RW9ovmsqI_Q5JB8QBNSEJbRakZO0ccYnwghjPDiBJ3mVU6rmrEJep673q63GwirdqskdFZhqXrrHfYGa-tjZ90llljZPgwRm1b-9M5bfYltxNbpQYHG_Tr4YbXG4LRfgfMJ_Pvn3--X8R42a-sSifs0Bd-mtLXfIVXLBvo0Lcg-nqFjI9sI5_tzih6_3DwsvmXLu6-3i_kyUzmr6kwbljeFkhIaTZsUSd5UJi_rhuSUc15BY2oJOeNG0qLQujQMOK0oV2rcxRR93vVugv8xQOxFZ6OCtpUO0qfF6IqXBSvrhF7vUBV8jAGM2ATbybAVlIjRvRhNi9G0eHOfXnzalw9NB_rAv8tOANsBv2wL2__1icXN_a74FSl7k2E</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Hsu, Chia‐Chen</creator><creator>Lin, Mang Hung</creator><creator>Cheng, Juei Tang</creator><creator>Wu, Ming Chang</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4522-584X</orcidid></search><sort><creationdate>201705</creationdate><title>Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats</title><author>Hsu, Chia‐Chen ; Lin, Mang Hung ; Cheng, Juei Tang ; Wu, Ming Chang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2589-df52b3caaebd1b258a6b8f249b0216668ebf9ae256fa133dd4f5e61816cc16cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>beta-Endorphin - blood</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Citrus</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 1 - drug therapy</topic><topic>diosmin</topic><topic>Diosmin - pharmacology</topic><topic>Diosmin - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flavonoids - pharmacology</topic><topic>Flavonoids - therapeutic use</topic><topic>Hyperglycemia - blood</topic><topic>Hyperglycemia - drug therapy</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Male</topic><topic>opioid receptor</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>STZ‐diabetic rats</topic><topic>β‐endorphin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, Chia‐Chen</creatorcontrib><creatorcontrib>Lin, Mang Hung</creatorcontrib><creatorcontrib>Cheng, Juei Tang</creatorcontrib><creatorcontrib>Wu, Ming Chang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental pharmacology & physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, Chia‐Chen</au><au>Lin, Mang Hung</au><au>Cheng, Juei Tang</au><au>Wu, Ming Chang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats</atitle><jtitle>Clinical and experimental pharmacology & physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2017-05</date><risdate>2017</risdate><volume>44</volume><issue>5</issue><spage>549</spage><epage>555</epage><pages>549-555</pages><issn>0305-1870</issn><eissn>1440-1681</eissn><abstract>Summary
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.</abstract><cop>Australia</cop><pmid>28218955</pmid><doi>10.1111/1440-1681.12739</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4522-584X</orcidid></addata></record> |
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| subjects | Animals beta-Endorphin - blood Blood Glucose - drug effects Blood Glucose - metabolism Citrus Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - drug therapy diosmin Diosmin - pharmacology Diosmin - therapeutic use Dose-Response Relationship, Drug Flavonoids - pharmacology Flavonoids - therapeutic use Hyperglycemia - blood Hyperglycemia - drug therapy Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Male opioid receptor Rats Rats, Sprague-Dawley STZ‐diabetic rats β‐endorphin |
| title | Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats |
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