Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog
Objective Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions....
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| Veröffentlicht in: | Obesity (Silver Spring, Md.) Md.), 2014-05, Vol.22 (5), p.1238-1245 |
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| creator | Ader, Marilyn Stefanovski, Darko Kim, Stella P. Richey, Joyce M. Ionut, Viorica Catalano, Karyn J. Hucking, Katrin Ellmerer, Martin Citters, Gregg Hsu, Isabel R. Chiu, Jenny D. Woolcott, Orison O. Harrison, Lisa N. Zheng, Dan Lottati, Maya Kolka, Cathryn M. Mooradian, Vahe Dittmann, Justin Yae, Sophia Liu, Huiwen Castro, Ana Valeria B. Kabir, Morvarid Bergman, Richard N. |
| description | Objective
Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions.
Methods
Metabolic assessment was performed in healthy dogs (n = 90). Whole‐body sensitivity from euglycemic clamps (SICLAMP) was the primary outcome variable, and was measured independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and glucose‐stimulated insulin response was measured from hyperglycemic clamp or IVGTT (n = 86 and 36, respectively).
Results
SICLAMP was highly variable (5.9‐75.9 dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7 ± 0.3 kg), adiposity varied approximately eight‐fold and was inversely correlated with SICLAMP (P |
| doi_str_mv | 10.1002/oby.20625 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1521339014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1521339014</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4545-7e81ee58a23a42b044e94d7a8a065cb7f883f815f8b174a8d74fda27739f7f583</originalsourceid><addsrcrecordid>eNp1kEFLwzAUx4MoTqcHv4AUvOhhW5ImTXrUoU4Y7KKgBwlp-6IZbTqTVum3t25zB8HTezx-7897P4TOCB4TjOmkzroxxQnle-iIpDEeiTh93t_1kgzQcQhLjFmCOTlEA8oIjdNEHKHXGax0Y_PIutCW1kV5Cdprl0NkQ9S8Q7TyttK-iwpowFfWaddEtdnxAVywjf20TdfP1huu9pUuo6J-O0EHRpcBTrd1iJ7ubh-ns9F8cf8wvZ6PcsYZHwmQBIBLTWPNaIYZg5QVQkuNE55nwkgZG0m4kRkRTMtCMFNoKvo3jTBcxkN0ucld-fqjhdCoyoYcylI7qNugCKckjlNMWI9e_EGXdetdf50iieAkpbhnh-hqQ-W-DsGDUVsNimD141z1ztXaec-ebxPbrIJiR_5K7oHJBviyJXT_J6nFzcsm8huKdIr5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1675192021</pqid></control><display><type>article</type><title>Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog</title><source>MEDLINE</source><source>Wiley Free Content</source><source>Wiley Online Library All Journals</source><creator>Ader, Marilyn ; Stefanovski, Darko ; Kim, Stella P. ; Richey, Joyce M. ; Ionut, Viorica ; Catalano, Karyn J. ; Hucking, Katrin ; Ellmerer, Martin ; Citters, Gregg ; Hsu, Isabel R. ; Chiu, Jenny D. ; Woolcott, Orison O. ; Harrison, Lisa N. ; Zheng, Dan ; Lottati, Maya ; Kolka, Cathryn M. ; Mooradian, Vahe ; Dittmann, Justin ; Yae, Sophia ; Liu, Huiwen ; Castro, Ana Valeria B. ; Kabir, Morvarid ; Bergman, Richard N.</creator><creatorcontrib>Ader, Marilyn ; Stefanovski, Darko ; Kim, Stella P. ; Richey, Joyce M. ; Ionut, Viorica ; Catalano, Karyn J. ; Hucking, Katrin ; Ellmerer, Martin ; Citters, Gregg ; Hsu, Isabel R. ; Chiu, Jenny D. ; Woolcott, Orison O. ; Harrison, Lisa N. ; Zheng, Dan ; Lottati, Maya ; Kolka, Cathryn M. ; Mooradian, Vahe ; Dittmann, Justin ; Yae, Sophia ; Liu, Huiwen ; Castro, Ana Valeria B. ; Kabir, Morvarid ; Bergman, Richard N.</creatorcontrib><description>Objective
Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions.
Methods
Metabolic assessment was performed in healthy dogs (n = 90). Whole‐body sensitivity from euglycemic clamps (SICLAMP) was the primary outcome variable, and was measured independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and glucose‐stimulated insulin response was measured from hyperglycemic clamp or IVGTT (n = 86 and 36, respectively).
Results
SICLAMP was highly variable (5.9‐75.9 dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7 ± 0.3 kg), adiposity varied approximately eight‐fold and was inversely correlated with SICLAMP (P < 0.025). SICLAMP was negatively associated with fasting insulin, but most strongly associated with insulin clearance. Clearance was the dominant factor associated with sensitivity (r = 0.53, P < 0.00001), whether calculated from clamp or IVGTT.
Conclusions
These data suggest that insulin clearance contributes substantially to insulin sensitivity, and may be pivotal in understanding the pathogenesis of insulin resistance. We propose the hyperinsulinemia due to reduction in insulin clearance is responsible for insulin resistance secondary to changes in body weight.</description><identifier>ISSN: 1930-7381</identifier><identifier>EISSN: 1930-739X</identifier><identifier>DOI: 10.1002/oby.20625</identifier><identifier>PMID: 24123967</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Blood Glucose - metabolism ; Body Composition ; Body Mass Index ; Body Weight ; Diabetes Mellitus, Type 2 - blood ; Dogs ; Fasting ; Glucose ; Glucose Clamp Technique - methods ; Hyperglycemia ; Hyperinsulinism ; Insulin ; Insulin - blood ; Insulin resistance ; Insulin Resistance - physiology ; Liver - metabolism ; Magnetic Resonance Imaging ; Male ; Obesity ; Obesity - blood ; Rodents</subject><ispartof>Obesity (Silver Spring, Md.), 2014-05, Vol.22 (5), p.1238-1245</ispartof><rights>Copyright © 2013 The Obesity Society</rights><rights>Copyright © 2013 The Obesity Society.</rights><rights>Copyright Blackwell Publishing Ltd. May 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4545-7e81ee58a23a42b044e94d7a8a065cb7f883f815f8b174a8d74fda27739f7f583</citedby><cites>FETCH-LOGICAL-c4545-7e81ee58a23a42b044e94d7a8a065cb7f883f815f8b174a8d74fda27739f7f583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Foby.20625$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Foby.20625$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,1435,27931,27932,45581,45582,46416,46840</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24123967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ader, Marilyn</creatorcontrib><creatorcontrib>Stefanovski, Darko</creatorcontrib><creatorcontrib>Kim, Stella P.</creatorcontrib><creatorcontrib>Richey, Joyce M.</creatorcontrib><creatorcontrib>Ionut, Viorica</creatorcontrib><creatorcontrib>Catalano, Karyn J.</creatorcontrib><creatorcontrib>Hucking, Katrin</creatorcontrib><creatorcontrib>Ellmerer, Martin</creatorcontrib><creatorcontrib>Citters, Gregg</creatorcontrib><creatorcontrib>Hsu, Isabel R.</creatorcontrib><creatorcontrib>Chiu, Jenny D.</creatorcontrib><creatorcontrib>Woolcott, Orison O.</creatorcontrib><creatorcontrib>Harrison, Lisa N.</creatorcontrib><creatorcontrib>Zheng, Dan</creatorcontrib><creatorcontrib>Lottati, Maya</creatorcontrib><creatorcontrib>Kolka, Cathryn M.</creatorcontrib><creatorcontrib>Mooradian, Vahe</creatorcontrib><creatorcontrib>Dittmann, Justin</creatorcontrib><creatorcontrib>Yae, Sophia</creatorcontrib><creatorcontrib>Liu, Huiwen</creatorcontrib><creatorcontrib>Castro, Ana Valeria B.</creatorcontrib><creatorcontrib>Kabir, Morvarid</creatorcontrib><creatorcontrib>Bergman, Richard N.</creatorcontrib><title>Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog</title><title>Obesity (Silver Spring, Md.)</title><addtitle>Obesity (Silver Spring)</addtitle><description>Objective
Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions.
Methods
Metabolic assessment was performed in healthy dogs (n = 90). Whole‐body sensitivity from euglycemic clamps (SICLAMP) was the primary outcome variable, and was measured independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and glucose‐stimulated insulin response was measured from hyperglycemic clamp or IVGTT (n = 86 and 36, respectively).
Results
SICLAMP was highly variable (5.9‐75.9 dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7 ± 0.3 kg), adiposity varied approximately eight‐fold and was inversely correlated with SICLAMP (P < 0.025). SICLAMP was negatively associated with fasting insulin, but most strongly associated with insulin clearance. Clearance was the dominant factor associated with sensitivity (r = 0.53, P < 0.00001), whether calculated from clamp or IVGTT.
Conclusions
These data suggest that insulin clearance contributes substantially to insulin sensitivity, and may be pivotal in understanding the pathogenesis of insulin resistance. We propose the hyperinsulinemia due to reduction in insulin clearance is responsible for insulin resistance secondary to changes in body weight.</description><subject>Animals</subject><subject>Blood Glucose - metabolism</subject><subject>Body Composition</subject><subject>Body Mass Index</subject><subject>Body Weight</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Dogs</subject><subject>Fasting</subject><subject>Glucose</subject><subject>Glucose Clamp Technique - methods</subject><subject>Hyperglycemia</subject><subject>Hyperinsulinism</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - physiology</subject><subject>Liver - metabolism</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Obesity</subject><subject>Obesity - blood</subject><subject>Rodents</subject><issn>1930-7381</issn><issn>1930-739X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAUx4MoTqcHv4AUvOhhW5ImTXrUoU4Y7KKgBwlp-6IZbTqTVum3t25zB8HTezx-7897P4TOCB4TjOmkzroxxQnle-iIpDEeiTh93t_1kgzQcQhLjFmCOTlEA8oIjdNEHKHXGax0Y_PIutCW1kV5Cdprl0NkQ9S8Q7TyttK-iwpowFfWaddEtdnxAVywjf20TdfP1huu9pUuo6J-O0EHRpcBTrd1iJ7ubh-ns9F8cf8wvZ6PcsYZHwmQBIBLTWPNaIYZg5QVQkuNE55nwkgZG0m4kRkRTMtCMFNoKvo3jTBcxkN0ucld-fqjhdCoyoYcylI7qNugCKckjlNMWI9e_EGXdetdf50iieAkpbhnh-hqQ-W-DsGDUVsNimD141z1ztXaec-ebxPbrIJiR_5K7oHJBviyJXT_J6nFzcsm8huKdIr5</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Ader, Marilyn</creator><creator>Stefanovski, Darko</creator><creator>Kim, Stella P.</creator><creator>Richey, Joyce M.</creator><creator>Ionut, Viorica</creator><creator>Catalano, Karyn J.</creator><creator>Hucking, Katrin</creator><creator>Ellmerer, Martin</creator><creator>Citters, Gregg</creator><creator>Hsu, Isabel R.</creator><creator>Chiu, Jenny D.</creator><creator>Woolcott, Orison O.</creator><creator>Harrison, Lisa N.</creator><creator>Zheng, Dan</creator><creator>Lottati, Maya</creator><creator>Kolka, Cathryn M.</creator><creator>Mooradian, Vahe</creator><creator>Dittmann, Justin</creator><creator>Yae, Sophia</creator><creator>Liu, Huiwen</creator><creator>Castro, Ana Valeria B.</creator><creator>Kabir, Morvarid</creator><creator>Bergman, Richard N.</creator><general>Blackwell Publishing 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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201405</creationdate><title>Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog</title><author>Ader, Marilyn ; Stefanovski, Darko ; Kim, Stella P. ; Richey, Joyce M. ; Ionut, Viorica ; Catalano, Karyn J. ; Hucking, Katrin ; Ellmerer, Martin ; Citters, Gregg ; Hsu, Isabel R. ; Chiu, Jenny D. ; Woolcott, Orison O. ; Harrison, Lisa N. ; Zheng, Dan ; Lottati, Maya ; Kolka, Cathryn M. ; Mooradian, Vahe ; Dittmann, Justin ; Yae, Sophia ; Liu, Huiwen ; Castro, Ana Valeria B. ; Kabir, Morvarid ; Bergman, Richard N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4545-7e81ee58a23a42b044e94d7a8a065cb7f883f815f8b174a8d74fda27739f7f583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Blood Glucose - metabolism</topic><topic>Body Composition</topic><topic>Body Mass Index</topic><topic>Body Weight</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Dogs</topic><topic>Fasting</topic><topic>Glucose</topic><topic>Glucose Clamp Technique - methods</topic><topic>Hyperglycemia</topic><topic>Hyperinsulinism</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - physiology</topic><topic>Liver - metabolism</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Obesity</topic><topic>Obesity - blood</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ader, Marilyn</creatorcontrib><creatorcontrib>Stefanovski, Darko</creatorcontrib><creatorcontrib>Kim, Stella P.</creatorcontrib><creatorcontrib>Richey, Joyce M.</creatorcontrib><creatorcontrib>Ionut, Viorica</creatorcontrib><creatorcontrib>Catalano, Karyn J.</creatorcontrib><creatorcontrib>Hucking, Katrin</creatorcontrib><creatorcontrib>Ellmerer, Martin</creatorcontrib><creatorcontrib>Citters, Gregg</creatorcontrib><creatorcontrib>Hsu, Isabel R.</creatorcontrib><creatorcontrib>Chiu, Jenny D.</creatorcontrib><creatorcontrib>Woolcott, Orison O.</creatorcontrib><creatorcontrib>Harrison, Lisa N.</creatorcontrib><creatorcontrib>Zheng, Dan</creatorcontrib><creatorcontrib>Lottati, Maya</creatorcontrib><creatorcontrib>Kolka, Cathryn M.</creatorcontrib><creatorcontrib>Mooradian, Vahe</creatorcontrib><creatorcontrib>Dittmann, Justin</creatorcontrib><creatorcontrib>Yae, Sophia</creatorcontrib><creatorcontrib>Liu, Huiwen</creatorcontrib><creatorcontrib>Castro, Ana Valeria B.</creatorcontrib><creatorcontrib>Kabir, Morvarid</creatorcontrib><creatorcontrib>Bergman, Richard N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ader, Marilyn</au><au>Stefanovski, Darko</au><au>Kim, Stella P.</au><au>Richey, Joyce M.</au><au>Ionut, Viorica</au><au>Catalano, Karyn J.</au><au>Hucking, Katrin</au><au>Ellmerer, Martin</au><au>Citters, Gregg</au><au>Hsu, Isabel R.</au><au>Chiu, Jenny D.</au><au>Woolcott, Orison O.</au><au>Harrison, Lisa N.</au><au>Zheng, Dan</au><au>Lottati, Maya</au><au>Kolka, Cathryn M.</au><au>Mooradian, Vahe</au><au>Dittmann, Justin</au><au>Yae, Sophia</au><au>Liu, Huiwen</au><au>Castro, Ana Valeria B.</au><au>Kabir, Morvarid</au><au>Bergman, Richard N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obesity (Silver Spring)</addtitle><date>2014-05</date><risdate>2014</risdate><volume>22</volume><issue>5</issue><spage>1238</spage><epage>1245</epage><pages>1238-1245</pages><issn>1930-7381</issn><eissn>1930-739X</eissn><abstract>Objective
Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, nonstimulated conditions.
Methods
Metabolic assessment was performed in healthy dogs (n = 90). Whole‐body sensitivity from euglycemic clamps (SICLAMP) was the primary outcome variable, and was measured independently by IVGTT (n = 36). Adiposity was measured by MRI (n = 90), and glucose‐stimulated insulin response was measured from hyperglycemic clamp or IVGTT (n = 86 and 36, respectively).
Results
SICLAMP was highly variable (5.9‐75.9 dl/min per kg per μU/ml). Despite narrow range of body weight (mean, 28.7 ± 0.3 kg), adiposity varied approximately eight‐fold and was inversely correlated with SICLAMP (P < 0.025). SICLAMP was negatively associated with fasting insulin, but most strongly associated with insulin clearance. Clearance was the dominant factor associated with sensitivity (r = 0.53, P < 0.00001), whether calculated from clamp or IVGTT.
Conclusions
These data suggest that insulin clearance contributes substantially to insulin sensitivity, and may be pivotal in understanding the pathogenesis of insulin resistance. We propose the hyperinsulinemia due to reduction in insulin clearance is responsible for insulin resistance secondary to changes in body weight.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24123967</pmid><doi>10.1002/oby.20625</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1930-7381 |
| ispartof | Obesity (Silver Spring, Md.), 2014-05, Vol.22 (5), p.1238-1245 |
| issn | 1930-7381 1930-739X |
| language | eng |
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| source | MEDLINE; Wiley Free Content; Wiley Online Library All Journals |
| subjects | Animals Blood Glucose - metabolism Body Composition Body Mass Index Body Weight Diabetes Mellitus, Type 2 - blood Dogs Fasting Glucose Glucose Clamp Technique - methods Hyperglycemia Hyperinsulinism Insulin Insulin - blood Insulin resistance Insulin Resistance - physiology Liver - metabolism Magnetic Resonance Imaging Male Obesity Obesity - blood Rodents |
| title | Hepatic insulin clearance is the primary determinant of insulin sensitivity in the normal dog |
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