Hypoglycemic effect of S(−)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide
A short-lasting hypoglycemic effect was observed when S(−)-hydroxyhexamide ( S-HH), a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide ( R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administ...
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| Veröffentlicht in: | Life sciences (1973) 2001-09, Vol.69 (16), p.1947-1955 |
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| container_end_page | 1955 |
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| container_issue | 16 |
| container_start_page | 1947 |
| container_title | Life sciences (1973) |
| container_volume | 69 |
| creator | Imamura, Yorishige Sanai, Kazuko Seri, Kenji Akita, Hiroyuki |
| description | A short-lasting hypoglycemic effect was observed when
S(−)-hydroxyhexamide (
S-HH), a major metabolite of acetohexamide, and its enantiomer
R(+)-hydroxyhexamide (
R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of
R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of
R-HH to rabbits, in spite of their inability to oxidize
R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both
S-HH and
R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic β-cells). These results provide further evidence that both
R-HH and
S-HH exhibit a significant hypoglycemic effect. |
| doi_str_mv | 10.1016/S0024-3205(01)01284-X |
| format | Article |
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S(−)-hydroxyhexamide (
S-HH), a major metabolite of acetohexamide, and its enantiomer
R(+)-hydroxyhexamide (
R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of
R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of
R-HH to rabbits, in spite of their inability to oxidize
R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both
S-HH and
R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic β-cells). These results provide further evidence that both
R-HH and
S-HH exhibit a significant hypoglycemic effect.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/S0024-3205(01)01284-X</identifier><identifier>PMID: 11693275</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Acetohexamide - administration & dosage ; Acetohexamide - analogs & derivatives ; Acetohexamide - metabolism ; Acetohexamide - pharmacology ; Administration, Oral ; Animals ; Blood Glucose - drug effects ; Cricetinae ; Dose-Response Relationship, Drug ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - pharmacology ; Hypoglycemic effect ; Insulin - analysis ; Insulin - blood ; Insulin secretion ; Islets of Langerhans - cytology ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Male ; R(+)-Hydroxyhexamide ; Rabbits ; Rats ; Rats, Wistar ; S(−)-Hydroxyhexamide ; Stereoisomerism ; Time Factors</subject><ispartof>Life sciences (1973), 2001-09, Vol.69 (16), p.1947-1955</ispartof><rights>2001 Elsevier Science Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-d508aa449eff2e4056d9dcfc7c4d5d17fe0db3c8c2b37cf0491c036089e2adcd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0024-3205(01)01284-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11693275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Imamura, Yorishige</creatorcontrib><creatorcontrib>Sanai, Kazuko</creatorcontrib><creatorcontrib>Seri, Kenji</creatorcontrib><creatorcontrib>Akita, Hiroyuki</creatorcontrib><title>Hypoglycemic effect of S(−)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>A short-lasting hypoglycemic effect was observed when
S(−)-hydroxyhexamide (
S-HH), a major metabolite of acetohexamide, and its enantiomer
R(+)-hydroxyhexamide (
R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of
R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of
R-HH to rabbits, in spite of their inability to oxidize
R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both
S-HH and
R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic β-cells). These results provide further evidence that both
R-HH and
S-HH exhibit a significant hypoglycemic effect.</description><subject>Acetohexamide - administration & dosage</subject><subject>Acetohexamide - analogs & derivatives</subject><subject>Acetohexamide - metabolism</subject><subject>Acetohexamide - pharmacology</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Blood Glucose - drug effects</subject><subject>Cricetinae</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypoglycemic effect</subject><subject>Insulin - analysis</subject><subject>Insulin - blood</subject><subject>Insulin secretion</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Male</subject><subject>R(+)-Hydroxyhexamide</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>S(−)-Hydroxyhexamide</subject><subject>Stereoisomerism</subject><subject>Time Factors</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1rFEEQhhsxmE30J0T6JBt0tPpjvk4hBDWBgGAUcmt6q2uSDjPTm-7ZkCF_IGd_or_E2eyiggdPdXnqfasexg4EvBcgig8XAFJnSkI-B3EIQlY6u3zGZqIq6wwKJZ6z2W9kl-2ldAMAeV6qF2xXiKJWssxn7OF0XIardkTqPHJqGsKBh4ZfzH8-_jjMrkcXw_14Tfe2847eccs7exMi72iwi9D6gda0RRrCX1DvuB8Sp972gw8dRf51_vaftJdsp7Ftolfbuc--f_r47eQ0O__y-ezk-DxDVYghczlU1mpdT9dJ0pAXrnbYYIna5U6UDYFbKKxQLlSJDehaIKgCqpqkdejUPnuzyV3GcLuiNJjOJ6S2tT2FVTKllFrLopjAfANiDClFaswy-s7G0Qgwa-vmybpZKzUgzJN1czntvd4WrBYduT9bW80TcLQBaHrzzlM0CT31SM7HSbhxwf-n4heXNZTM</recordid><startdate>20010907</startdate><enddate>20010907</enddate><creator>Imamura, Yorishige</creator><creator>Sanai, Kazuko</creator><creator>Seri, Kenji</creator><creator>Akita, Hiroyuki</creator><general>Elsevier Inc</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>20010907</creationdate><title>Hypoglycemic effect of S(−)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide</title><author>Imamura, Yorishige ; Sanai, Kazuko ; Seri, Kenji ; Akita, Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-d508aa449eff2e4056d9dcfc7c4d5d17fe0db3c8c2b37cf0491c036089e2adcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acetohexamide - administration & dosage</topic><topic>Acetohexamide - analogs & derivatives</topic><topic>Acetohexamide - metabolism</topic><topic>Acetohexamide - pharmacology</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Blood Glucose - drug effects</topic><topic>Cricetinae</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Hypoglycemic effect</topic><topic>Insulin - analysis</topic><topic>Insulin - blood</topic><topic>Insulin secretion</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Male</topic><topic>R(+)-Hydroxyhexamide</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>S(−)-Hydroxyhexamide</topic><topic>Stereoisomerism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Imamura, Yorishige</creatorcontrib><creatorcontrib>Sanai, Kazuko</creatorcontrib><creatorcontrib>Seri, Kenji</creatorcontrib><creatorcontrib>Akita, Hiroyuki</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>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Imamura, Yorishige</au><au>Sanai, Kazuko</au><au>Seri, Kenji</au><au>Akita, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoglycemic effect of S(−)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2001-09-07</date><risdate>2001</risdate><volume>69</volume><issue>16</issue><spage>1947</spage><epage>1955</epage><pages>1947-1955</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>A short-lasting hypoglycemic effect was observed when
S(−)-hydroxyhexamide (
S-HH), a major metabolite of acetohexamide, and its enantiomer
R(+)-hydroxyhexamide (
R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of
R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of
R-HH to rabbits, in spite of their inability to oxidize
R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both
S-HH and
R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic β-cells). These results provide further evidence that both
R-HH and
S-HH exhibit a significant hypoglycemic effect.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>11693275</pmid><doi>10.1016/S0024-3205(01)01284-X</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Life sciences (1973), 2001-09, Vol.69 (16), p.1947-1955 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acetohexamide - administration & dosage Acetohexamide - analogs & derivatives Acetohexamide - metabolism Acetohexamide - pharmacology Administration, Oral Animals Blood Glucose - drug effects Cricetinae Dose-Response Relationship, Drug Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - pharmacology Hypoglycemic effect Insulin - analysis Insulin - blood Insulin secretion Islets of Langerhans - cytology Islets of Langerhans - drug effects Islets of Langerhans - metabolism Male R(+)-Hydroxyhexamide Rabbits Rats Rats, Wistar S(−)-Hydroxyhexamide Stereoisomerism Time Factors |
| title | Hypoglycemic effect of S(−)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide |
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