Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss
Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvemen...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2021-10, Vol.70 (10), p.2289-2298 |
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| creator | Ben-Haroush Schyr, Rachel Al-Kurd, Abbas Moalem, Botros Permyakova, Anna Israeli, Hadar Bardugo, Aya Arad, Yhara Hefetz, Liron Bergel, Michael Haran, Arnon Azar, Shahar Magenheim, Itia Tam, Joseph Grinbaum, Ronit Ben-Zvi, Danny |
| description | Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet. |
| doi_str_mv | 10.2337/db21-0251 |
| format | Article |
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It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db21-0251</identifier><identifier>PMID: 34341005</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Animals ; Bariatric Surgery ; Blood vessels ; Body weight loss ; Diabetes ; Fatty liver ; Gastrectomy ; Gastrectomy - methods ; Gastrointestinal surgery ; Glucagon ; Glucose ; Glucose - metabolism ; High fat diet ; Insulin ; Insulin - metabolism ; Insulin Resistance - physiology ; Liver - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Obese ; Obesity - metabolism ; Obesity - surgery ; Obesity Studies ; Portal vein ; Steatosis ; Sucrose ; Surgery ; Weight Loss - physiology</subject><ispartof>Diabetes (New York, N.Y.), 2021-10, Vol.70 (10), p.2289-2298</ispartof><rights>2021 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Oct 1, 2021</rights><rights>2021 by the American Diabetes Association 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-5b106c5f57ef3967b16e366937fea4d9bca66a7841ab46f410994cb821e31b213</citedby><cites>FETCH-LOGICAL-c403t-5b106c5f57ef3967b16e366937fea4d9bca66a7841ab46f410994cb821e31b213</cites><orcidid>0000-0002-8697-9744</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576500/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576500/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34341005$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ben-Haroush Schyr, Rachel</creatorcontrib><creatorcontrib>Al-Kurd, Abbas</creatorcontrib><creatorcontrib>Moalem, Botros</creatorcontrib><creatorcontrib>Permyakova, Anna</creatorcontrib><creatorcontrib>Israeli, Hadar</creatorcontrib><creatorcontrib>Bardugo, Aya</creatorcontrib><creatorcontrib>Arad, Yhara</creatorcontrib><creatorcontrib>Hefetz, Liron</creatorcontrib><creatorcontrib>Bergel, Michael</creatorcontrib><creatorcontrib>Haran, Arnon</creatorcontrib><creatorcontrib>Azar, Shahar</creatorcontrib><creatorcontrib>Magenheim, Itia</creatorcontrib><creatorcontrib>Tam, Joseph</creatorcontrib><creatorcontrib>Grinbaum, Ronit</creatorcontrib><creatorcontrib>Ben-Zvi, Danny</creatorcontrib><title>Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet.</description><subject>Animals</subject><subject>Bariatric Surgery</subject><subject>Blood vessels</subject><subject>Body weight loss</subject><subject>Diabetes</subject><subject>Fatty liver</subject><subject>Gastrectomy</subject><subject>Gastrectomy - methods</subject><subject>Gastrointestinal surgery</subject><subject>Glucagon</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>High fat diet</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance - physiology</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred ICR</subject><subject>Mice, Obese</subject><subject>Obesity - metabolism</subject><subject>Obesity - surgery</subject><subject>Obesity Studies</subject><subject>Portal vein</subject><subject>Steatosis</subject><subject>Sucrose</subject><subject>Surgery</subject><subject>Weight Loss - physiology</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU9r3DAQxUVpaDabHvoFiqCX5uB0ZFmSfSmUJdldWEggDclNyPI4cfBKrmQHQr58tOQPSRnQwOjH4808Qr4xOM45V7-aOmcZ5IJ9IjNW8Srjubr-TGYALM-YqtQ-OYjxDgBkqi9knxe8YABiRh4vesR7pEsTx4B29NsHejENQ8AYMdIVDmbsLF32k_UR6XnwzWTHzjtqXEPXzgY078G1i1PfObro0QTjLKZJgwOmx43Ut_QKu5vbkW58jIdkrzV9xK8vfU4uT0_-LlbZ5my5XvzZZLYAPmaiZiCtaIXClldS1Uwil7LiqkVTNFVtjZRGlQUzdSHbtFhVFbYuc4acpcvwOfn9rDtM9RYbm5wE0-shdFsTHrQ3nf7447pbfePvdSmUFABJ4OeLQPD_Joyj3nbRYt8bh36KOhdCCQEK8oT--A-981Nwab1ElQCqULxM1NEzZUO6Q8D2zQwDvYtU7yLVu0gT-_29-zfyNUP-BJWqnZU</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Ben-Haroush Schyr, Rachel</creator><creator>Al-Kurd, Abbas</creator><creator>Moalem, Botros</creator><creator>Permyakova, Anna</creator><creator>Israeli, Hadar</creator><creator>Bardugo, Aya</creator><creator>Arad, Yhara</creator><creator>Hefetz, Liron</creator><creator>Bergel, Michael</creator><creator>Haran, Arnon</creator><creator>Azar, Shahar</creator><creator>Magenheim, Itia</creator><creator>Tam, Joseph</creator><creator>Grinbaum, Ronit</creator><creator>Ben-Zvi, Danny</creator><general>American Diabetes Association</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>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8697-9744</orcidid></search><sort><creationdate>20211001</creationdate><title>Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss</title><author>Ben-Haroush Schyr, Rachel ; 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It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>34341005</pmid><doi>10.2337/db21-0251</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8697-9744</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Bariatric Surgery Blood vessels Body weight loss Diabetes Fatty liver Gastrectomy Gastrectomy - methods Gastrointestinal surgery Glucagon Glucose Glucose - metabolism High fat diet Insulin Insulin - metabolism Insulin Resistance - physiology Liver - metabolism Male Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Obese Obesity - metabolism Obesity - surgery Obesity Studies Portal vein Steatosis Sucrose Surgery Weight Loss - physiology |
| title | Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss |
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