Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet
Eating a "Westernized" diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerh...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2013-10, Vol.62 (10), p.3500-3513 |
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| creator | FIORI, Jennifer L SHIN, Yu-Kyong DOYLE, Maire E PEARSON, Kevin J MATTISON, Julie A DE CABO, Rafael EGAN, Josephine M WOOK KIM KRZYSIK-WALKER, Susan M GONZALEZ-MARISCAL, Isabel CARLSON, Olga D SANGHVI, Mitesh MOADDEL, Ruin FARHANG, Kathleen GADKAREE, Shekhar K |
| description | Eating a "Westernized" diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes. |
| doi_str_mv | 10.2337/db13-0266 |
| format | Article |
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Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db13-0266</identifier><identifier>PMID: 23884882</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; Blood sugar ; Body Weight ; Cell Dedifferentiation ; Densitometry ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - genetics ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes. Impaired glucose tolerance ; Diet, High-Fat ; Dietary Sucrose ; Disease Models, Animal ; Dosage and administration ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fluorescent Antibody Technique ; Glucagon - metabolism ; Glucagon-Like Peptide 1 - metabolism ; Glucagon-Secreting Cells - drug effects ; Glucagon-Secreting Cells - metabolism ; Glucose Tolerance Test ; Glycated Hemoglobin A - metabolism ; Health aspects ; Insulin - metabolism ; Insulin Resistance ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - pathology ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; Macaca mulatta ; Medical sciences ; Original Research ; Pancreatic beta cells ; Physiological aspects ; Protective Agents - administration & dosage ; Protective Agents - pharmacology ; Resveratrol ; Sirtuin 1 - metabolism ; Stilbenes - administration & dosage ; Stilbenes - pharmacology</subject><ispartof>Diabetes (New York, N.Y.), 2013-10, Vol.62 (10), p.3500-3513</ispartof><rights>2014 INIST-CNRS</rights><rights>COPYRIGHT 2013 American Diabetes Association</rights><rights>2013 by the American Diabetes Association. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c544t-9ecf09404eaeb859bf9488c8cb29d5cdc1f1dd4737db1e2ca963fc1ec4bac7053</citedby><cites>FETCH-LOGICAL-c544t-9ecf09404eaeb859bf9488c8cb29d5cdc1f1dd4737db1e2ca963fc1ec4bac7053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781448/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781448/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27784733$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23884882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FIORI, Jennifer L</creatorcontrib><creatorcontrib>SHIN, Yu-Kyong</creatorcontrib><creatorcontrib>DOYLE, Maire E</creatorcontrib><creatorcontrib>PEARSON, Kevin J</creatorcontrib><creatorcontrib>MATTISON, Julie A</creatorcontrib><creatorcontrib>DE CABO, Rafael</creatorcontrib><creatorcontrib>EGAN, Josephine M</creatorcontrib><creatorcontrib>WOOK KIM</creatorcontrib><creatorcontrib>KRZYSIK-WALKER, Susan M</creatorcontrib><creatorcontrib>GONZALEZ-MARISCAL, Isabel</creatorcontrib><creatorcontrib>CARLSON, Olga D</creatorcontrib><creatorcontrib>SANGHVI, Mitesh</creatorcontrib><creatorcontrib>MOADDEL, Ruin</creatorcontrib><creatorcontrib>FARHANG, Kathleen</creatorcontrib><creatorcontrib>GADKAREE, Shekhar K</creatorcontrib><title>Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Eating a "Westernized" diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Blood sugar</subject><subject>Body Weight</subject><subject>Cell Dedifferentiation</subject><subject>Densitometry</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - genetics</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet, High-Fat</subject><subject>Dietary Sucrose</subject><subject>Disease Models, Animal</subject><subject>Dosage and administration</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Fluorescent Antibody Technique</subject><subject>Glucagon - metabolism</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Glucagon-Secreting Cells - drug effects</subject><subject>Glucagon-Secreting Cells - metabolism</subject><subject>Glucose Tolerance Test</subject><subject>Glycated Hemoglobin A - metabolism</subject><subject>Health aspects</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Insulin-Secreting Cells - pathology</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>Macaca mulatta</subject><subject>Medical sciences</subject><subject>Original Research</subject><subject>Pancreatic beta cells</subject><subject>Physiological aspects</subject><subject>Protective Agents - administration & dosage</subject><subject>Protective Agents - pharmacology</subject><subject>Resveratrol</subject><subject>Sirtuin 1 - metabolism</subject><subject>Stilbenes - administration & dosage</subject><subject>Stilbenes - pharmacology</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptks9u1DAQxi0EokvhwAugSAgJDmnt2IntS6VqS7dIK0D8kbhZjjPOGiVOsZNV-1o8CM-EQ5fCSqs52Br_5vP48yD0nOCTglJ-2tSE5rioqgdoQSSVOS34t4dogTEpcsIlP0JPYvyOMa5SPEZHBRWCCVEsUPMJ4haCHsPQZR8DbMGPMfv1M19C12UX0DhrIaSk06MbfOZ89n7wm6nXPuGu1yPEbOVSWaazK9du8ks9nv7ZfJ5aHbILB-NT9MjqLsKz3XqMvl6-_bK8ytcfVu-W5-vclIyNuQRjsWSYgYZalLK2MjVphKkL2ZSmMcSSpmGc8vRgKIyWFbWGgGG1NhyX9Bid3eleT3UPjUltB92p67nPcKsG7dT-iXcb1Q5bRbkgjIkk8HonEIYfE8RR9S6a5IT2MExREUY5IRKL-a6Xd2irO1DO2yEpmhlX5zRpFVVZzYL5AaoFnyzvBg_WpfQef3KAT9FA78zBgjd7BYkZ4WZs9RSjEqv1QdaEIcYA9t4ZgtU8SGoeJDUPUmJf_G_lPfl3chLwagfoaHRng_bGxX8c5yL9FKW_ASOJ0Do</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>FIORI, Jennifer L</creator><creator>SHIN, Yu-Kyong</creator><creator>DOYLE, Maire E</creator><creator>PEARSON, Kevin J</creator><creator>MATTISON, Julie A</creator><creator>DE CABO, Rafael</creator><creator>EGAN, Josephine M</creator><creator>WOOK KIM</creator><creator>KRZYSIK-WALKER, Susan M</creator><creator>GONZALEZ-MARISCAL, Isabel</creator><creator>CARLSON, Olga D</creator><creator>SANGHVI, Mitesh</creator><creator>MOADDEL, Ruin</creator><creator>FARHANG, Kathleen</creator><creator>GADKAREE, Shekhar K</creator><general>American Diabetes Association</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>8GL</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet</title><author>FIORI, Jennifer L ; SHIN, Yu-Kyong ; DOYLE, Maire E ; PEARSON, Kevin J ; MATTISON, Julie A ; DE CABO, Rafael ; EGAN, Josephine M ; WOOK KIM ; KRZYSIK-WALKER, Susan M ; GONZALEZ-MARISCAL, Isabel ; CARLSON, Olga D ; SANGHVI, Mitesh ; MOADDEL, Ruin ; FARHANG, Kathleen ; GADKAREE, Shekhar K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-9ecf09404eaeb859bf9488c8cb29d5cdc1f1dd4737db1e2ca963fc1ec4bac7053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Blood sugar</topic><topic>Body Weight</topic><topic>Cell Dedifferentiation</topic><topic>Densitometry</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - genetics</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet, High-Fat</topic><topic>Dietary Sucrose</topic><topic>Disease Models, Animal</topic><topic>Dosage and administration</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Fluorescent Antibody Technique</topic><topic>Glucagon - metabolism</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Glucagon-Secreting Cells - drug effects</topic><topic>Glucagon-Secreting Cells - metabolism</topic><topic>Glucose Tolerance Test</topic><topic>Glycated Hemoglobin A - metabolism</topic><topic>Health aspects</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Insulin-Secreting Cells - pathology</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>Macaca mulatta</topic><topic>Medical sciences</topic><topic>Original Research</topic><topic>Pancreatic beta cells</topic><topic>Physiological aspects</topic><topic>Protective Agents - administration & dosage</topic><topic>Protective Agents - pharmacology</topic><topic>Resveratrol</topic><topic>Sirtuin 1 - metabolism</topic><topic>Stilbenes - administration & dosage</topic><topic>Stilbenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FIORI, Jennifer L</creatorcontrib><creatorcontrib>SHIN, Yu-Kyong</creatorcontrib><creatorcontrib>DOYLE, Maire E</creatorcontrib><creatorcontrib>PEARSON, Kevin J</creatorcontrib><creatorcontrib>MATTISON, Julie A</creatorcontrib><creatorcontrib>DE CABO, Rafael</creatorcontrib><creatorcontrib>EGAN, Josephine M</creatorcontrib><creatorcontrib>WOOK KIM</creatorcontrib><creatorcontrib>KRZYSIK-WALKER, Susan M</creatorcontrib><creatorcontrib>GONZALEZ-MARISCAL, Isabel</creatorcontrib><creatorcontrib>CARLSON, Olga D</creatorcontrib><creatorcontrib>SANGHVI, Mitesh</creatorcontrib><creatorcontrib>MOADDEL, Ruin</creatorcontrib><creatorcontrib>FARHANG, Kathleen</creatorcontrib><creatorcontrib>GADKAREE, Shekhar K</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>Gale In Context: High School</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FIORI, Jennifer L</au><au>SHIN, Yu-Kyong</au><au>DOYLE, Maire E</au><au>PEARSON, Kevin J</au><au>MATTISON, Julie A</au><au>DE CABO, Rafael</au><au>EGAN, Josephine M</au><au>WOOK KIM</au><au>KRZYSIK-WALKER, Susan M</au><au>GONZALEZ-MARISCAL, Isabel</au><au>CARLSON, Olga D</au><au>SANGHVI, Mitesh</au><au>MOADDEL, Ruin</au><au>FARHANG, Kathleen</au><au>GADKAREE, Shekhar K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>62</volume><issue>10</issue><spage>3500</spage><epage>3513</epage><pages>3500-3513</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Eating a "Westernized" diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>23884882</pmid><doi>10.2337/db13-0266</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetes (New York, N.Y.), 2013-10, Vol.62 (10), p.3500-3513 |
| issn | 0012-1797 1939-327X |
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| source | MEDLINE; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Biological and medical sciences Blood Glucose - metabolism Blood sugar Body Weight Cell Dedifferentiation Densitometry Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes. Impaired glucose tolerance Diet, High-Fat Dietary Sucrose Disease Models, Animal Dosage and administration Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Fluorescent Antibody Technique Glucagon - metabolism Glucagon-Like Peptide 1 - metabolism Glucagon-Secreting Cells - drug effects Glucagon-Secreting Cells - metabolism Glucose Tolerance Test Glycated Hemoglobin A - metabolism Health aspects Insulin - metabolism Insulin Resistance Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Islets of Langerhans - drug effects Islets of Langerhans - metabolism Macaca mulatta Medical sciences Original Research Pancreatic beta cells Physiological aspects Protective Agents - administration & dosage Protective Agents - pharmacology Resveratrol Sirtuin 1 - metabolism Stilbenes - administration & dosage Stilbenes - pharmacology |
| title | Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet |
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