Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway
We examined whether acute in vivo increases in either plasma glucose or insulin concentrations stimulate PAI-1 gene expression in fat tissue. We studied chronically catheterized unstressed and awake, lean (∼300 g, n=12) and obese (∼450 g, n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced...
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| Veröffentlicht in: | Atherosclerosis 2002, Vol.160 (1), p.115-122 |
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| creator | Gabriely, Ilan Yang, Xiao Man Cases, Jane A Ma, Xiao Hui Rossetti, Luciano Barzilai, Nir |
| description | We examined whether acute in vivo increases in either plasma glucose or insulin concentrations stimulate PAI-1 gene expression in fat tissue. We studied chronically catheterized unstressed and awake, lean (∼300 g,
n=12) and obese (∼450 g,
n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced for 3 h by glucose infusion during a pancreatic clamp (somatostatin inhibited endogenous insulin secretion). Compared with equivalent saline infusion, hyperglycemia induced a 6–7 fold increase in PAI-1 gene expression in both lean and obese rats (
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| doi_str_mv | 10.1016/S0021-9150(01)00574-3 |
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n=12) and obese (∼450 g,
n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced for 3 h by glucose infusion during a pancreatic clamp (somatostatin inhibited endogenous insulin secretion). Compared with equivalent saline infusion, hyperglycemia induced a 6–7 fold increase in PAI-1 gene expression in both lean and obese rats (
P<0.001). When the rate of cellular glucose uptake was matched during a euglycemic hyperinsulinemic (∼60 μU/ml) clamp, PAI-1 gene expression in both obese and lean rats was proportionately and significantly increased (
P<0.001). We further examined whether induction of the hexosamine biosynthetic pathway would mimic the effects of hyperglycemia and hyperinsulinemia on PAI-1 gene expression. Indeed, infusion of glucosamine (GlcN, 30 μmol/kg/min), induced a ∼3–4 fold increase (
P<0.01) in PAI-1 gene expression in both lean and obese animals. While obese rats had a four times greater fat mass then the lean rats, PAI-1 gene expression remained significantly higher when expressed as per gram fat. Our results support the hypothesis that increased glucose uptake induces PAI-1 gene expression in adipose tissue, probably through the activation of the hexosamine biosynthetic pathway. These findings may account for some of the fibrinolytic alterations seen in obese type 2 diabetic humans.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/S0021-9150(01)00574-3</identifier><identifier>PMID: 11755928</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Adipose Tissue - metabolism ; Animals ; Biological and medical sciences ; Biotransformation - drug effects ; Blood Glucose - analysis ; Blood Glucose - drug effects ; Body Composition - drug effects ; Body Weight - drug effects ; Diabetes mellitus ; Gene Expression Regulation - drug effects ; Glucosamine - pharmacokinetics ; Glucose ; Hexosamine biosynthetic pathway ; Hexosamines - biosynthesis ; Hyperglycemia - metabolism ; Insulin - blood ; Insulin Resistance ; Male ; Medical sciences ; Metabolic diseases ; Obesity ; Plasminogen Activator Inhibitor 1 - genetics ; Plasminogen activator inhibitor type-1 ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride - pharmacokinetics</subject><ispartof>Atherosclerosis, 2002, Vol.160 (1), p.115-122</ispartof><rights>2002 Elsevier Science Ireland Ltd</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-42522c1be975c875438f6762d05b042dcf7803fc72fe454949a5ffcf3781ba8b3</citedby><cites>FETCH-LOGICAL-c391t-42522c1be975c875438f6762d05b042dcf7803fc72fe454949a5ffcf3781ba8b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915001005743$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13430900$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11755928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gabriely, Ilan</creatorcontrib><creatorcontrib>Yang, Xiao Man</creatorcontrib><creatorcontrib>Cases, Jane A</creatorcontrib><creatorcontrib>Ma, Xiao Hui</creatorcontrib><creatorcontrib>Rossetti, Luciano</creatorcontrib><creatorcontrib>Barzilai, Nir</creatorcontrib><title>Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>We examined whether acute in vivo increases in either plasma glucose or insulin concentrations stimulate PAI-1 gene expression in fat tissue. We studied chronically catheterized unstressed and awake, lean (∼300 g,
n=12) and obese (∼450 g,
n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced for 3 h by glucose infusion during a pancreatic clamp (somatostatin inhibited endogenous insulin secretion). Compared with equivalent saline infusion, hyperglycemia induced a 6–7 fold increase in PAI-1 gene expression in both lean and obese rats (
P<0.001). When the rate of cellular glucose uptake was matched during a euglycemic hyperinsulinemic (∼60 μU/ml) clamp, PAI-1 gene expression in both obese and lean rats was proportionately and significantly increased (
P<0.001). We further examined whether induction of the hexosamine biosynthetic pathway would mimic the effects of hyperglycemia and hyperinsulinemia on PAI-1 gene expression. Indeed, infusion of glucosamine (GlcN, 30 μmol/kg/min), induced a ∼3–4 fold increase (
P<0.01) in PAI-1 gene expression in both lean and obese animals. While obese rats had a four times greater fat mass then the lean rats, PAI-1 gene expression remained significantly higher when expressed as per gram fat. Our results support the hypothesis that increased glucose uptake induces PAI-1 gene expression in adipose tissue, probably through the activation of the hexosamine biosynthetic pathway. These findings may account for some of the fibrinolytic alterations seen in obese type 2 diabetic humans.</description><subject>Adipose Tissue - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotransformation - drug effects</subject><subject>Blood Glucose - analysis</subject><subject>Blood Glucose - drug effects</subject><subject>Body Composition - drug effects</subject><subject>Body Weight - drug effects</subject><subject>Diabetes mellitus</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glucosamine - pharmacokinetics</subject><subject>Glucose</subject><subject>Hexosamine biosynthetic pathway</subject><subject>Hexosamines - biosynthesis</subject><subject>Hyperglycemia - metabolism</subject><subject>Insulin - blood</subject><subject>Insulin Resistance</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Obesity</subject><subject>Plasminogen Activator Inhibitor 1 - genetics</subject><subject>Plasminogen activator inhibitor type-1</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sodium Chloride - pharmacokinetics</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotvCTwD5AiqHwDi21_EJVRXQSpVAAs6W44y7RvnCk5Tm35PtruiR00gzzzszehh7JeC9ALH98B2gFIUVGs5BvAPQRhXyCduIythCqEo9ZZt_yAk7JfoFAMqI6jk7EcJobctqw_LVMmK-bZeAXfI89c0ckPi3i-tC8FvskeP9mJEoDf065b5J40DIp0Q0I68X7sOU7vy0nw-RTzvkO7wfyHdpDddpoKVfm1MKfPTT7o9fXrBn0beEL4_1jP38_OnH5VVx8_XL9eXFTRGkFVOhSl2WQdRojQ6V0UpWcWu2ZQO6BlU2IZoKZAymjKi0ssp6HWOI0lSi9lUtz9jbw94xD79npMl1iQK2re9xmMkZIZWy2q6gPoAhD0QZoxtz6nxenAC3l-0eZLu9SQfCPch2cs29Ph6Y6w6bx9TR7gq8OQKegm9j9n1I9MhJJcECrNzHA4erjruE2VFI2AdsUsYwuWZI_3nlL7xfnKA</recordid><startdate>2002</startdate><enddate>2002</enddate><creator>Gabriely, Ilan</creator><creator>Yang, Xiao Man</creator><creator>Cases, Jane A</creator><creator>Ma, Xiao Hui</creator><creator>Rossetti, Luciano</creator><creator>Barzilai, Nir</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</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>2002</creationdate><title>Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway</title><author>Gabriely, Ilan ; Yang, Xiao Man ; Cases, Jane A ; Ma, Xiao Hui ; Rossetti, Luciano ; Barzilai, Nir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-42522c1be975c875438f6762d05b042dcf7803fc72fe454949a5ffcf3781ba8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adipose Tissue - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotransformation - drug effects</topic><topic>Blood Glucose - analysis</topic><topic>Blood Glucose - drug effects</topic><topic>Body Composition - drug effects</topic><topic>Body Weight - drug effects</topic><topic>Diabetes mellitus</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Glucosamine - pharmacokinetics</topic><topic>Glucose</topic><topic>Hexosamine biosynthetic pathway</topic><topic>Hexosamines - biosynthesis</topic><topic>Hyperglycemia - metabolism</topic><topic>Insulin - blood</topic><topic>Insulin Resistance</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Obesity</topic><topic>Plasminogen Activator Inhibitor 1 - genetics</topic><topic>Plasminogen activator inhibitor type-1</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sodium Chloride - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gabriely, Ilan</creatorcontrib><creatorcontrib>Yang, Xiao Man</creatorcontrib><creatorcontrib>Cases, Jane A</creatorcontrib><creatorcontrib>Ma, Xiao Hui</creatorcontrib><creatorcontrib>Rossetti, Luciano</creatorcontrib><creatorcontrib>Barzilai, Nir</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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gabriely, Ilan</au><au>Yang, Xiao Man</au><au>Cases, Jane A</au><au>Ma, Xiao Hui</au><au>Rossetti, Luciano</au><au>Barzilai, Nir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2002</date><risdate>2002</risdate><volume>160</volume><issue>1</issue><spage>115</spage><epage>122</epage><pages>115-122</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>We examined whether acute in vivo increases in either plasma glucose or insulin concentrations stimulate PAI-1 gene expression in fat tissue. We studied chronically catheterized unstressed and awake, lean (∼300 g,
n=12) and obese (∼450 g,
n=12) Sprague–Dawley rats. Hyperglycemia (∼ 18mM) was induced for 3 h by glucose infusion during a pancreatic clamp (somatostatin inhibited endogenous insulin secretion). Compared with equivalent saline infusion, hyperglycemia induced a 6–7 fold increase in PAI-1 gene expression in both lean and obese rats (
P<0.001). When the rate of cellular glucose uptake was matched during a euglycemic hyperinsulinemic (∼60 μU/ml) clamp, PAI-1 gene expression in both obese and lean rats was proportionately and significantly increased (
P<0.001). We further examined whether induction of the hexosamine biosynthetic pathway would mimic the effects of hyperglycemia and hyperinsulinemia on PAI-1 gene expression. Indeed, infusion of glucosamine (GlcN, 30 μmol/kg/min), induced a ∼3–4 fold increase (
P<0.01) in PAI-1 gene expression in both lean and obese animals. While obese rats had a four times greater fat mass then the lean rats, PAI-1 gene expression remained significantly higher when expressed as per gram fat. Our results support the hypothesis that increased glucose uptake induces PAI-1 gene expression in adipose tissue, probably through the activation of the hexosamine biosynthetic pathway. These findings may account for some of the fibrinolytic alterations seen in obese type 2 diabetic humans.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>11755928</pmid><doi>10.1016/S0021-9150(01)00574-3</doi><tpages>8</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adipose Tissue - metabolism Animals Biological and medical sciences Biotransformation - drug effects Blood Glucose - analysis Blood Glucose - drug effects Body Composition - drug effects Body Weight - drug effects Diabetes mellitus Gene Expression Regulation - drug effects Glucosamine - pharmacokinetics Glucose Hexosamine biosynthetic pathway Hexosamines - biosynthesis Hyperglycemia - metabolism Insulin - blood Insulin Resistance Male Medical sciences Metabolic diseases Obesity Plasminogen Activator Inhibitor 1 - genetics Plasminogen activator inhibitor type-1 Rats Rats, Sprague-Dawley Sodium Chloride - pharmacokinetics |
| title | Hyperglycemia induces PAI-1 gene expression in adipose tissue by activation of the hexosamine biosynthetic pathway |
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