Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677)
A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the ec 50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguani...
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| Veröffentlicht in: | Biochemical pharmacology 1990-10, Vol.40 (8), p.1821-1825 |
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| creator | Kühnle, H.F. Wolff, H.P. Schmidt, F.H. Reiter, R. |
| description | A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the
ec
50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig ⪢ mouse > rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate > pyruvate > alanine ⪢ propionate > glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (
ec
50 = 0.85
mM
) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug. |
| doi_str_mv | 10.1016/0006-2952(90)90362-O |
| format | Article |
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ec
50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig ⪢ mouse > rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate > pyruvate > alanine ⪢ propionate > glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (
ec
50 = 0.85
mM
) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(90)90362-O</identifier><identifier>PMID: 2242016</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cells, Cultured ; Fasting ; General and cellular metabolism. Vitamins ; Gluconeogenesis - drug effects ; Guinea Pigs ; Hypoglycemic Agents - pharmacology ; Imino Acids - administration & dosage ; Imino Acids - pharmacology ; Liver - drug effects ; Male ; Medical sciences ; Metformin - pharmacology ; Mice ; Pharmacology. Drug treatments ; Phenformin - pharmacology ; Rabbits ; Rats</subject><ispartof>Biochemical pharmacology, 1990-10, Vol.40 (8), p.1821-1825</ispartof><rights>1990</rights><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-976761a6629227e7254c7f6957624efd3dd79579b6639ddaab6ee6639ceebe0c3</citedby><cites>FETCH-LOGICAL-c387t-976761a6629227e7254c7f6957624efd3dd79579b6639ddaab6ee6639ceebe0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/000629529090362O$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19327790$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2242016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kühnle, H.F.</creatorcontrib><creatorcontrib>Wolff, H.P.</creatorcontrib><creatorcontrib>Schmidt, F.H.</creatorcontrib><creatorcontrib>Reiter, R.</creatorcontrib><title>Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677)</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the
ec
50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig ⪢ mouse > rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate > pyruvate > alanine ⪢ propionate > glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (
ec
50 = 0.85
mM
) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Fasting</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Gluconeogenesis - drug effects</subject><subject>Guinea Pigs</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Imino Acids - administration & dosage</subject><subject>Imino Acids - pharmacology</subject><subject>Liver - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metformin - pharmacology</subject><subject>Mice</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenformin - pharmacology</subject><subject>Rabbits</subject><subject>Rats</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PGzEQhq2KKk1D_wGV9gJKDqb-SOz1BQlQW5BShQOcLa89C64269Tehe6_x9tEcOvJnpl3Ho0ehE4oOaeEim-EEIGZWrG5IgtFuGB48wFNaSl5bovyCE3fIp_Q55R-j2Up6ARNGFuyzJiiu6smBIcfm96GBLgJLxB9-1gY2_ln3w1FqAuG5xzvnqAdml0Mu_B38FvvwgJXfTdE00Exv_pVUH4upFwco4-1aRJ8Obwz9PDj-_31DV5vft5eX66x5aXssJJCCmqEYIoxCZKtllbWQq2kYEuoHXdO5kJVQnDlnDGVABj_FqACYvkMne25-aQ_PaROb32y0DSmhdAnXRJKZcl5Di73QRtDShFqvYt-a-KgKdGjSD1q0aMlrYj-J1Jv8trXA7-vtuDelg7m8vz0MDfJmqaOprU-vbMVZ1Jm2Axd7HOQZTx7iDpZD60F5yPYTrvg_3_IKwZ9jQk</recordid><startdate>19901015</startdate><enddate>19901015</enddate><creator>Kühnle, H.F.</creator><creator>Wolff, H.P.</creator><creator>Schmidt, F.H.</creator><creator>Reiter, R.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><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>19901015</creationdate><title>Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677)</title><author>Kühnle, H.F. ; Wolff, H.P. ; Schmidt, F.H. ; Reiter, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-976761a6629227e7254c7f6957624efd3dd79579b6639ddaab6ee6639ceebe0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Fasting</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Gluconeogenesis - drug effects</topic><topic>Guinea Pigs</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Imino Acids - administration & dosage</topic><topic>Imino Acids - pharmacology</topic><topic>Liver - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metformin - pharmacology</topic><topic>Mice</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenformin - pharmacology</topic><topic>Rabbits</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kühnle, H.F.</creatorcontrib><creatorcontrib>Wolff, H.P.</creatorcontrib><creatorcontrib>Schmidt, F.H.</creatorcontrib><creatorcontrib>Reiter, R.</creatorcontrib><collection>Pascal-Francis</collection><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>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kühnle, H.F.</au><au>Wolff, H.P.</au><au>Schmidt, F.H.</au><au>Reiter, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677)</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1990-10-15</date><risdate>1990</risdate><volume>40</volume><issue>8</issue><spage>1821</spage><epage>1825</epage><pages>1821-1825</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the
ec
50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig ⪢ mouse > rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate > pyruvate > alanine ⪢ propionate > glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (
ec
50 = 0.85
mM
) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>2242016</pmid><doi>10.1016/0006-2952(90)90362-O</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cells, Cultured Fasting General and cellular metabolism. Vitamins Gluconeogenesis - drug effects Guinea Pigs Hypoglycemic Agents - pharmacology Imino Acids - administration & dosage Imino Acids - pharmacology Liver - drug effects Male Medical sciences Metformin - pharmacology Mice Pharmacology. Drug treatments Phenformin - pharmacology Rabbits Rats |
| title | Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) |
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