Effect of corosolic acid on gluconeogenesis in rat liver
Abstract Corosolic acid (CRA), an active component of Banaba leaves ( Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 μM) dose-dependently decreased gluconeo...
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| Veröffentlicht in: | Diabetes research and clinical practice 2008-04, Vol.80 (1), p.48-55 |
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| creator | Yamada, Kotaro Hosokawa, Masaya Fujimoto, Shimpei Fujiwara, Hideya Fujita, Yoshihito Harada, Norio Yamada, Chizumi Fukushima, Mitsuo Ueda, Naoya Kaneko, Tetsuo Matsuyama, Futoshi Yamada, Yuichiro Seino, Yutaka Inagaki, Nobuya |
| description | Abstract Corosolic acid (CRA), an active component of Banaba leaves ( Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 μM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA. |
| doi_str_mv | 10.1016/j.diabres.2007.11.011 |
| format | Article |
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In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 μM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.</description><identifier>ISSN: 0168-8227</identifier><identifier>EISSN: 1872-8227</identifier><identifier>DOI: 10.1016/j.diabres.2007.11.011</identifier><identifier>PMID: 18177973</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; cAMP ; Carbon Radioisotopes ; Corosolic acid ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Endocrinology & Metabolism ; Fructose-2,6-bisphosphate ; Fructosediphosphates - biosynthesis ; Gluconeogenesis ; Gluconeogenesis - drug effects ; Glucose - biosynthesis ; Glucose-6-Phosphatase - metabolism ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Isoquinolines - pharmacology ; Lactic Acid - metabolism ; Liver ; Liver - drug effects ; Liver - metabolism ; Musa - chemistry ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Plant Leaves - chemistry ; Protein Kinase Inhibitors - pharmacology ; Rats ; Rats, Wistar ; Sulfonamides - pharmacology ; Triterpenes - chemistry ; Triterpenes - pharmacology</subject><ispartof>Diabetes research and clinical practice, 2008-04, Vol.80 (1), p.48-55</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-f49d0f440de65979afc119db5ac803459f524dc1f61ce96c0c308913dfba5da23</citedby><cites>FETCH-LOGICAL-c484t-f49d0f440de65979afc119db5ac803459f524dc1f61ce96c0c308913dfba5da23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168822707006055$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18177973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Kotaro</creatorcontrib><creatorcontrib>Hosokawa, Masaya</creatorcontrib><creatorcontrib>Fujimoto, Shimpei</creatorcontrib><creatorcontrib>Fujiwara, Hideya</creatorcontrib><creatorcontrib>Fujita, Yoshihito</creatorcontrib><creatorcontrib>Harada, Norio</creatorcontrib><creatorcontrib>Yamada, Chizumi</creatorcontrib><creatorcontrib>Fukushima, Mitsuo</creatorcontrib><creatorcontrib>Ueda, Naoya</creatorcontrib><creatorcontrib>Kaneko, Tetsuo</creatorcontrib><creatorcontrib>Matsuyama, Futoshi</creatorcontrib><creatorcontrib>Yamada, Yuichiro</creatorcontrib><creatorcontrib>Seino, Yutaka</creatorcontrib><creatorcontrib>Inagaki, Nobuya</creatorcontrib><title>Effect of corosolic acid on gluconeogenesis in rat liver</title><title>Diabetes research and clinical practice</title><addtitle>Diabetes Res Clin Pract</addtitle><description>Abstract Corosolic acid (CRA), an active component of Banaba leaves ( Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 μM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.</description><subject>Animals</subject><subject>cAMP</subject><subject>Carbon Radioisotopes</subject><subject>Corosolic acid</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Endocrinology & Metabolism</subject><subject>Fructose-2,6-bisphosphate</subject><subject>Fructosediphosphates - biosynthesis</subject><subject>Gluconeogenesis</subject><subject>Gluconeogenesis - drug effects</subject><subject>Glucose - biosynthesis</subject><subject>Glucose-6-Phosphatase - metabolism</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Isoquinolines - pharmacology</subject><subject>Lactic Acid - metabolism</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Musa - chemistry</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Leaves - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sulfonamides - pharmacology</subject><subject>Triterpenes - chemistry</subject><subject>Triterpenes - pharmacology</subject><issn>0168-8227</issn><issn>1872-8227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQhq2qVdnS_oSinLhtOpM4sXMBIQS0ElIP0LPlHY-Rt9kY7A0S_x5vdyUkLj3Zh2e-nleI7wg1AvY_1rULdpU41w2AqhFrQPwgFqhVs9RNoz6KReH0v_-R-JLzGgD6VnafxRFqVGpQ7ULoK--ZtlX0FcUUcxwDVZaCq-JUPYwzxYnjA0-cQ67CVCW7rcbwzOmr-OTtmPnb4T0Wf66v7i9_Lm9_3_y6vLhdktRyu_RycOClBMd9N6jBekIc3KqzpKEsM_iukY7Q90g89ATUgh6wdX5lO2eb9lic7vs-pvg0c96aTcjE42jLYnM2CmQrG9AF7PYglTNyYm8eU9jY9GIQzE6ZWZuDMrNTZhBNUVbqTg4D5tWG3VvVwVEBzvcAlzOfAyeTKfBE7EIq6oyL4b8jzt51oDFMgez4l184r-OcpuLQoMmNAXO3y20XG6iSGHRd-wrRGpPE</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>Yamada, Kotaro</creator><creator>Hosokawa, Masaya</creator><creator>Fujimoto, Shimpei</creator><creator>Fujiwara, Hideya</creator><creator>Fujita, Yoshihito</creator><creator>Harada, Norio</creator><creator>Yamada, Chizumi</creator><creator>Fukushima, Mitsuo</creator><creator>Ueda, Naoya</creator><creator>Kaneko, Tetsuo</creator><creator>Matsuyama, Futoshi</creator><creator>Yamada, Yuichiro</creator><creator>Seino, Yutaka</creator><creator>Inagaki, Nobuya</creator><general>Elsevier Ireland Ltd</general><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></search><sort><creationdate>20080401</creationdate><title>Effect of corosolic acid on gluconeogenesis in rat liver</title><author>Yamada, Kotaro ; Hosokawa, Masaya ; Fujimoto, Shimpei ; Fujiwara, Hideya ; Fujita, Yoshihito ; Harada, Norio ; Yamada, Chizumi ; Fukushima, Mitsuo ; Ueda, Naoya ; Kaneko, Tetsuo ; Matsuyama, Futoshi ; Yamada, Yuichiro ; Seino, Yutaka ; Inagaki, Nobuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-f49d0f440de65979afc119db5ac803459f524dc1f61ce96c0c308913dfba5da23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>cAMP</topic><topic>Carbon Radioisotopes</topic><topic>Corosolic acid</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Endocrinology & Metabolism</topic><topic>Fructose-2,6-bisphosphate</topic><topic>Fructosediphosphates - biosynthesis</topic><topic>Gluconeogenesis</topic><topic>Gluconeogenesis - drug effects</topic><topic>Glucose - biosynthesis</topic><topic>Glucose-6-Phosphatase - metabolism</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Isoquinolines - pharmacology</topic><topic>Lactic Acid - metabolism</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Musa - chemistry</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Leaves - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sulfonamides - pharmacology</topic><topic>Triterpenes - chemistry</topic><topic>Triterpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Kotaro</creatorcontrib><creatorcontrib>Hosokawa, Masaya</creatorcontrib><creatorcontrib>Fujimoto, Shimpei</creatorcontrib><creatorcontrib>Fujiwara, Hideya</creatorcontrib><creatorcontrib>Fujita, Yoshihito</creatorcontrib><creatorcontrib>Harada, Norio</creatorcontrib><creatorcontrib>Yamada, Chizumi</creatorcontrib><creatorcontrib>Fukushima, Mitsuo</creatorcontrib><creatorcontrib>Ueda, Naoya</creatorcontrib><creatorcontrib>Kaneko, Tetsuo</creatorcontrib><creatorcontrib>Matsuyama, Futoshi</creatorcontrib><creatorcontrib>Yamada, Yuichiro</creatorcontrib><creatorcontrib>Seino, Yutaka</creatorcontrib><creatorcontrib>Inagaki, Nobuya</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>Diabetes research and clinical practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Kotaro</au><au>Hosokawa, Masaya</au><au>Fujimoto, Shimpei</au><au>Fujiwara, Hideya</au><au>Fujita, Yoshihito</au><au>Harada, Norio</au><au>Yamada, Chizumi</au><au>Fukushima, Mitsuo</au><au>Ueda, Naoya</au><au>Kaneko, Tetsuo</au><au>Matsuyama, Futoshi</au><au>Yamada, Yuichiro</au><au>Seino, Yutaka</au><au>Inagaki, Nobuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of corosolic acid on gluconeogenesis in rat liver</atitle><jtitle>Diabetes research and clinical practice</jtitle><addtitle>Diabetes Res Clin Pract</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>80</volume><issue>1</issue><spage>48</spage><epage>55</epage><pages>48-55</pages><issn>0168-8227</issn><eissn>1872-8227</eissn><abstract>Abstract Corosolic acid (CRA), an active component of Banaba leaves ( Lagerstroemia speciosa L.), decreases blood glucose in diabetic animals and humans. In this study, we investigated the mechanism of action of CRA on gluconeogenesis in rat liver. CRA (20–100 μM) dose-dependently decreased gluconeogenesis in perfused liver and in isolated hepatocytes. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. CRA increased the production of F-2,6-BP along with a decrease in intracellular levels of cAMP both in the presence and in the absence of forskolin in isolated hepatocytes. While a cAMP-dependent protein kinase (PKA) inhibitor inhibited hepatic gluconeogenesis, the drug did not intensify the inhibitory effect of CRA on hepatic gluconeogenesis in isolated hepatocytes. These results indicate that CRA inhibits gluconeogenesis by increasing the production of F-2,6-BP by lowering the cAMP level and inhibiting PKA activity in isolated hepatocytes. Furthermore, CRA increased glucokinase activity in isolated hepatocytes without affecting glucose-6-phosphatase activity, suggesting the promotion of glycolysis. These effects on hepatic glucose metabolism may underlie the various anti-diabetic actions of CRA.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18177973</pmid><doi>10.1016/j.diabres.2007.11.011</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals cAMP Carbon Radioisotopes Corosolic acid Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - metabolism Endocrinology & Metabolism Fructose-2,6-bisphosphate Fructosediphosphates - biosynthesis Gluconeogenesis Gluconeogenesis - drug effects Glucose - biosynthesis Glucose-6-Phosphatase - metabolism Hepatocytes - drug effects Hepatocytes - metabolism Isoquinolines - pharmacology Lactic Acid - metabolism Liver Liver - drug effects Liver - metabolism Musa - chemistry Plant Extracts - chemistry Plant Extracts - pharmacology Plant Leaves - chemistry Protein Kinase Inhibitors - pharmacology Rats Rats, Wistar Sulfonamides - pharmacology Triterpenes - chemistry Triterpenes - pharmacology |
| title | Effect of corosolic acid on gluconeogenesis in rat liver |
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