Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05-01

AUTHORS

Midori Honma, Shojiro Sawada, Yoshiyuki Ueno, Keigo Murakami, Tetsuya Yamada, Junhong Gao, Shinjiro Kodama, Tomohito Izumi, Kei Takahashi, Sohei Tsukita, Kenji Uno, Junta Imai, Eiji Kakazu, Yasuteru Kondo, Kei Mizuno, Naoki Kawagishi, Tooru Shimosegawa, Hideki Katagiri

ABSTRACT

Background/objective:Insulin signals, via the regulation of key enzyme expression, both suppress gluconeogenesis and enhance lipid synthesis in the liver. Animal studies have revealed insulin signaling favoring gluconeogenesis suppression to be selectively impaired in steatotic livers. However, whether, and if so how, such selective insulin resistance occurs in human steatotic livers remains unknown. Our aim was to investigate selective insulin resistance in human livers with non-alcoholic fatty liver disease (NAFLD).Subjects/methods:We examined mRNA expressions of key molecules for insulin signaling, gluconeogenesis and lipogenesis in human liver biopsy samples obtained from 51 non-diabetic subjects: 9 healthy controls and 42 NAFLD patients, and analyzed associations of these molecules with each other and with detailed pathological and clinical biochemistry data.Results:In NAFLD patients, insulin receptor substrate (IRS)-2 expression was decreased, while those of key enzymes for gluconeogenesis were increased. These alterations of IRS-2 and gluconeogenesis enzymes were induced both in simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), while these expression levels did not differ between SS and NASH. Furthermore, alterations in the expressions of IRS-2 and gluconeogenesis enzymes showed strong negative correlations and were concurrently induced in the early histological stage of NAFLD. In contrast, fatty acid synthase (FAS) expression was not decreased in NAFLD, despite IRS-2 downregulation, but correlated strongly with IRS-1 expression. Furthermore, no histological scores were associated with these molecules. Thus, IRS-1 signaling, which is not impaired in NAFLD, appears to modulate FAS expression.Conclusion:These analyses revealed that selective insulin resistance is present in human NAFLD livers and occurs in its early phases. The effect of insulin, during the IRS step, on gene expressions for lipogenesis and gluconeogenesis are apparently distinct and preferential downregulation of IRS-2 may contribute to selective resistance to the suppressive effects of insulin on gluconeogenesis. More... »

PAGES

1544-1555

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41366-018-0062-9

DOI

http://dx.doi.org/10.1038/s41366-018-0062-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103689854

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29717275


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biopsy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Case-Control Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Insulin Receptor Substrate Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Insulin Resistance", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Liver", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Non-alcoholic Fatty Liver Disease", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Honma", 
        "givenName": "Midori", 
        "id": "sg:person.015433216133.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015433216133.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sawada", 
        "givenName": "Shojiro", 
        "id": "sg:person.01264270414.13", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264270414.13"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Japan Agency for Medical Research and Development, CREST, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.480536.c", 
          "name": [
            "Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan", 
            "Japan Agency for Medical Research and Development, CREST, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ueno", 
        "givenName": "Yoshiyuki", 
        "id": "sg:person.010427522032.32", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010427522032.32"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Murakami", 
        "givenName": "Keigo", 
        "id": "sg:person.01142407026.96", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142407026.96"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
            "Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yamada", 
        "givenName": "Tetsuya", 
        "id": "sg:person.01343321656.69", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01343321656.69"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gao", 
        "givenName": "Junhong", 
        "id": "sg:person.0722266435.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722266435.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kodama", 
        "givenName": "Shinjiro", 
        "id": "sg:person.01272145150.58", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272145150.58"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Izumi", 
        "givenName": "Tomohito", 
        "id": "sg:person.01030314210.81", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030314210.81"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Takahashi", 
        "givenName": "Kei", 
        "id": "sg:person.0646631700.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646631700.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tsukita", 
        "givenName": "Sohei", 
        "id": "sg:person.0603136414.81", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0603136414.81"
        ], 
        "type": "Person"
      }, 
      {
        "familyName": "Uno", 
        "givenName": "Kenji", 
        "id": "sg:person.0716766352.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716766352.19"
        ], 
        "type": "Person"
      }, 
      {
        "familyName": "Imai", 
        "givenName": "Junta", 
        "id": "sg:person.0643255040.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0643255040.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kakazu", 
        "givenName": "Eiji", 
        "id": "sg:person.0704634134.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704634134.00"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kondo", 
        "givenName": "Yasuteru", 
        "id": "sg:person.01264265721.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264265721.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan", 
          "id": "http://www.grid.ac/institutes/grid.268394.2", 
          "name": [
            "Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mizuno", 
        "givenName": "Kei", 
        "id": "sg:person.01164106722.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164106722.99"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.412757.2", 
          "name": [
            "Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kawagishi", 
        "givenName": "Naoki", 
        "id": "sg:person.01345464520.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01345464520.60"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan", 
            "Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shimosegawa", 
        "givenName": "Tooru", 
        "id": "sg:person.01255535707.76", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255535707.76"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan", 
          "id": "http://www.grid.ac/institutes/grid.69566.3a", 
          "name": [
            "Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan", 
            "Japan Agency for Medical Research and Development, CREST, Tokyo, Japan", 
            "Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Katagiri", 
        "givenName": "Hideki", 
        "id": "sg:person.01101503716.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101503716.31"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/ijo.2012.181", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009999572", 
          "https://doi.org/10.1038/ijo.2012.181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11892-009-0034-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011237758", 
          "https://doi.org/10.1007/s11892-009-0034-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00018-008-8322-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029759544", 
          "https://doi.org/10.1007/s00018-008-8322-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm4074", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020513835", 
          "https://doi.org/10.1038/nrm4074"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12038-010-0052-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025296298", 
          "https://doi.org/10.1007/s12038-010-0052-0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/hr.2014.20", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044401479", 
          "https://doi.org/10.1038/hr.2014.20"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1111/j.1572-0241.1999.01377.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015032643", 
          "https://doi.org/10.1111/j.1572-0241.1999.01377.x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm1662", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039117182", 
          "https://doi.org/10.1038/nm1662"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms12977", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036117907", 
          "https://doi.org/10.1038/ncomms12977"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/414799a", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000331422", 
          "https://doi.org/10.1038/414799a"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/hr.2013.80", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041803518", 
          "https://doi.org/10.1038/hr.2013.80"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-05-01", 
    "datePublishedReg": "2018-05-01", 
    "description": "Background/objective:Insulin signals, via the regulation of key enzyme expression, both suppress gluconeogenesis and enhance lipid synthesis in the liver. Animal studies have revealed insulin signaling favoring gluconeogenesis suppression to be selectively impaired in steatotic livers. However, whether, and if so how, such selective insulin resistance occurs in human steatotic livers remains unknown. Our aim was to investigate selective insulin resistance in human livers with non-alcoholic fatty liver disease (NAFLD).Subjects/methods:We examined mRNA expressions of key molecules for insulin signaling, gluconeogenesis and lipogenesis in human liver biopsy samples obtained from 51 non-diabetic subjects: 9 healthy controls and 42 NAFLD patients, and analyzed associations of these molecules with each other and with detailed pathological and clinical biochemistry data.Results:In NAFLD patients, insulin receptor substrate (IRS)-2 expression was decreased, while those of key enzymes for gluconeogenesis were increased. These alterations of IRS-2 and gluconeogenesis enzymes were induced both in simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), while these expression levels did not differ between SS and NASH. Furthermore, alterations in the expressions of IRS-2 and gluconeogenesis enzymes showed strong negative correlations and were concurrently induced in the early histological stage of NAFLD. In contrast, fatty acid synthase (FAS) expression was not decreased in NAFLD, despite IRS-2 downregulation, but correlated strongly with IRS-1 expression. Furthermore, no histological scores were associated with these molecules. Thus, IRS-1 signaling, which is not impaired in NAFLD, appears to modulate FAS expression.Conclusion:These analyses revealed that selective insulin resistance is present in human NAFLD livers and occurs in its early phases. The effect of insulin, during the IRS step, on gene expressions for lipogenesis and gluconeogenesis are apparently distinct and preferential downregulation of IRS-2 may contribute to selective resistance to the suppressive effects of insulin on gluconeogenesis.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/s41366-018-0062-9", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.9341932", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.6835318", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7522408", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.5909462", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.5915768", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7522407", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.7543051", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.6112009", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1035838", 
        "issn": [
          "0307-0565", 
          "1476-5497"
        ], 
        "name": "International Journal of Obesity", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "9", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "42"
      }
    ], 
    "keywords": [
      "non-alcoholic fatty liver disease", 
      "non-alcoholic steatohepatitis", 
      "selective insulin resistance", 
      "insulin resistance", 
      "simple steatosis", 
      "NAFLD patients", 
      "steatotic livers", 
      "NAFLD livers", 
      "IRS-2", 
      "human steatotic liver", 
      "early histological stages", 
      "fatty acid synthase expression", 
      "non-diabetic subjects", 
      "fatty liver disease", 
      "gluconeogenesis enzymes", 
      "liver biopsy samples", 
      "IRS-1 expression", 
      "effect of insulin", 
      "human liver biopsy samples", 
      "IRS-1 signaling", 
      "liver disease", 
      "healthy controls", 
      "histological stage", 
      "histological scores", 
      "insulin receptor substrate", 
      "synthase expression", 
      "animal studies", 
      "gluconeogenesis suppression", 
      "biopsy samples", 
      "suppressive effect", 
      "FAS expression", 
      "biochemistry data", 
      "clinical biochemistry data", 
      "mRNA expression", 
      "liver", 
      "human liver", 
      "insulin", 
      "preferential downregulation", 
      "insulin signaling", 
      "key molecules", 
      "enzyme expression", 
      "expression levels", 
      "patients", 
      "IRS-1", 
      "suppress gluconeogenesis", 
      "receptor substrate", 
      "gluconeogenesis", 
      "selective resistance", 
      "lipogenesis", 
      "early phase", 
      "lipid synthesis", 
      "insulin signal", 
      "downregulation", 
      "differential expression", 
      "negative correlation", 
      "strong negative correlation", 
      "expression", 
      "key enzyme expression", 
      "alterations", 
      "gene expression", 
      "signaling", 
      "steatohepatitis", 
      "steatosis", 
      "key enzyme", 
      "disease", 
      "resistance", 
      "scores", 
      "association", 
      "enzyme", 
      "subjects", 
      "effect", 
      "aim", 
      "suppression", 
      "levels", 
      "control", 
      "study", 
      "regulation", 
      "correlation", 
      "contrast", 
      "molecules", 
      "stage", 
      "samples", 
      "data", 
      "analysis", 
      "synthesis", 
      "phase", 
      "signals", 
      "step", 
      "substrate"
    ], 
    "name": "Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers", 
    "pagination": "1544-1555", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1103689854"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41366-018-0062-9"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29717275"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41366-018-0062-9", 
      "https://app.dimensions.ai/details/publication/pub.1103689854"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-08-04T17:07", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_765.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/s41366-018-0062-9"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41366-018-0062-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41366-018-0062-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41366-018-0062-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41366-018-0062-9'


 

This table displays all metadata directly associated to this object as RDF triples.

388 TRIPLES      21 PREDICATES      136 URIs      117 LITERALS      18 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41366-018-0062-9 schema:about N2dbee5817d154248b0ce9da6ea51d62a
2 N2ffc11db47a84a07a10320ae4d58f939
3 N3c81d8871da9421bbfcee3b5897b692f
4 N5e2c0c38b5054907b036f107a693d86c
5 N72a914f33af946de9c53cddd354b2e7e
6 N880aff6d85694093b309d3cd6fcf171a
7 Naaba6f52702841688264096b218a1a14
8 Nbe896a71c2824f1fb614b5c8cc55b826
9 Nd4107a58a67543f490fb365be52e5346
10 Nea02339a80f2484e85889d81bc7d4bed
11 Nfedd0fd5a0624cb5bc795476807b5df2
12 anzsrc-for:11
13 anzsrc-for:1103
14 schema:author N26cc92bab28b49cab88747fe91e94328
15 schema:citation sg:pub.10.1007/s00018-008-8322-9
16 sg:pub.10.1007/s11892-009-0034-5
17 sg:pub.10.1007/s12038-010-0052-0
18 sg:pub.10.1038/414799a
19 sg:pub.10.1038/hr.2013.80
20 sg:pub.10.1038/hr.2014.20
21 sg:pub.10.1038/ijo.2012.181
22 sg:pub.10.1038/ncomms12977
23 sg:pub.10.1038/nm1662
24 sg:pub.10.1038/nrm4074
25 sg:pub.10.1111/j.1572-0241.1999.01377.x
26 schema:datePublished 2018-05-01
27 schema:datePublishedReg 2018-05-01
28 schema:description Background/objective:Insulin signals, via the regulation of key enzyme expression, both suppress gluconeogenesis and enhance lipid synthesis in the liver. Animal studies have revealed insulin signaling favoring gluconeogenesis suppression to be selectively impaired in steatotic livers. However, whether, and if so how, such selective insulin resistance occurs in human steatotic livers remains unknown. Our aim was to investigate selective insulin resistance in human livers with non-alcoholic fatty liver disease (NAFLD).Subjects/methods:We examined mRNA expressions of key molecules for insulin signaling, gluconeogenesis and lipogenesis in human liver biopsy samples obtained from 51 non-diabetic subjects: 9 healthy controls and 42 NAFLD patients, and analyzed associations of these molecules with each other and with detailed pathological and clinical biochemistry data.Results:In NAFLD patients, insulin receptor substrate (IRS)-2 expression was decreased, while those of key enzymes for gluconeogenesis were increased. These alterations of IRS-2 and gluconeogenesis enzymes were induced both in simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), while these expression levels did not differ between SS and NASH. Furthermore, alterations in the expressions of IRS-2 and gluconeogenesis enzymes showed strong negative correlations and were concurrently induced in the early histological stage of NAFLD. In contrast, fatty acid synthase (FAS) expression was not decreased in NAFLD, despite IRS-2 downregulation, but correlated strongly with IRS-1 expression. Furthermore, no histological scores were associated with these molecules. Thus, IRS-1 signaling, which is not impaired in NAFLD, appears to modulate FAS expression.Conclusion:These analyses revealed that selective insulin resistance is present in human NAFLD livers and occurs in its early phases. The effect of insulin, during the IRS step, on gene expressions for lipogenesis and gluconeogenesis are apparently distinct and preferential downregulation of IRS-2 may contribute to selective resistance to the suppressive effects of insulin on gluconeogenesis.
29 schema:genre article
30 schema:isAccessibleForFree true
31 schema:isPartOf N961cf0c268534d74a6df31be4e41a3f6
32 Naff3da5ebc904189a7cdccb19239dd06
33 sg:journal.1035838
34 schema:keywords FAS expression
35 IRS-1
36 IRS-1 expression
37 IRS-1 signaling
38 IRS-2
39 NAFLD livers
40 NAFLD patients
41 aim
42 alterations
43 analysis
44 animal studies
45 association
46 biochemistry data
47 biopsy samples
48 clinical biochemistry data
49 contrast
50 control
51 correlation
52 data
53 differential expression
54 disease
55 downregulation
56 early histological stages
57 early phase
58 effect
59 effect of insulin
60 enzyme
61 enzyme expression
62 expression
63 expression levels
64 fatty acid synthase expression
65 fatty liver disease
66 gene expression
67 gluconeogenesis
68 gluconeogenesis enzymes
69 gluconeogenesis suppression
70 healthy controls
71 histological scores
72 histological stage
73 human liver
74 human liver biopsy samples
75 human steatotic liver
76 insulin
77 insulin receptor substrate
78 insulin resistance
79 insulin signal
80 insulin signaling
81 key enzyme
82 key enzyme expression
83 key molecules
84 levels
85 lipid synthesis
86 lipogenesis
87 liver
88 liver biopsy samples
89 liver disease
90 mRNA expression
91 molecules
92 negative correlation
93 non-alcoholic fatty liver disease
94 non-alcoholic steatohepatitis
95 non-diabetic subjects
96 patients
97 phase
98 preferential downregulation
99 receptor substrate
100 regulation
101 resistance
102 samples
103 scores
104 selective insulin resistance
105 selective resistance
106 signaling
107 signals
108 simple steatosis
109 stage
110 steatohepatitis
111 steatosis
112 steatotic livers
113 step
114 strong negative correlation
115 study
116 subjects
117 substrate
118 suppress gluconeogenesis
119 suppression
120 suppressive effect
121 synthase expression
122 synthesis
123 schema:name Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers
124 schema:pagination 1544-1555
125 schema:productId N100d98a60fa34ad9b566012e2d3ccdee
126 N3b2071ccb96e40bcb7ee1fa691a53a99
127 Nac767c6db3a0439bb7331258388873dd
128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103689854
129 https://doi.org/10.1038/s41366-018-0062-9
130 schema:sdDatePublished 2022-08-04T17:07
131 schema:sdLicense https://scigraph.springernature.com/explorer/license/
132 schema:sdPublisher N2ba910862a3248beb1de262217ac578f
133 schema:url https://doi.org/10.1038/s41366-018-0062-9
134 sgo:license sg:explorer/license/
135 sgo:sdDataset articles
136 rdf:type schema:ScholarlyArticle
137 N0cb27bfb24c34cf69a723c71b8b08224 rdf:first sg:person.010427522032.32
138 rdf:rest N7679753b5cb3498eb63f930f8d4b8fe1
139 N100d98a60fa34ad9b566012e2d3ccdee schema:name doi
140 schema:value 10.1038/s41366-018-0062-9
141 rdf:type schema:PropertyValue
142 N26cc92bab28b49cab88747fe91e94328 rdf:first sg:person.015433216133.49
143 rdf:rest N47f5cc9bcf8e49649b902c7a346c7a35
144 N2ba910862a3248beb1de262217ac578f schema:name Springer Nature - SN SciGraph project
145 rdf:type schema:Organization
146 N2dbee5817d154248b0ce9da6ea51d62a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name Humans
148 rdf:type schema:DefinedTerm
149 N2ffc11db47a84a07a10320ae4d58f939 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Adult
151 rdf:type schema:DefinedTerm
152 N3b2071ccb96e40bcb7ee1fa691a53a99 schema:name dimensions_id
153 schema:value pub.1103689854
154 rdf:type schema:PropertyValue
155 N3c81d8871da9421bbfcee3b5897b692f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Female
157 rdf:type schema:DefinedTerm
158 N46ea02da21914882acd3b7cccedf8db1 rdf:first sg:person.01255535707.76
159 rdf:rest Nd73a6643d8064b04ad9758ee6d0bab31
160 N47f5cc9bcf8e49649b902c7a346c7a35 rdf:first sg:person.01264270414.13
161 rdf:rest N0cb27bfb24c34cf69a723c71b8b08224
162 N4f9da0321cd549a491b0880200ce2742 rdf:first sg:person.01345464520.60
163 rdf:rest N46ea02da21914882acd3b7cccedf8db1
164 N5de17d7a94f64116b6d39db1260c1f47 rdf:first sg:person.01030314210.81
165 rdf:rest Nd18fdb55eb0f4a61b45510232eaa1378
166 N5e2c0c38b5054907b036f107a693d86c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name Non-alcoholic Fatty Liver Disease
168 rdf:type schema:DefinedTerm
169 N72a914f33af946de9c53cddd354b2e7e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
170 schema:name Biopsy
171 rdf:type schema:DefinedTerm
172 N7679753b5cb3498eb63f930f8d4b8fe1 rdf:first sg:person.01142407026.96
173 rdf:rest Na43114dabd884e019aabc610e68cfd08
174 N7748f04eacbf4bb9a460c92ca80ace26 rdf:first sg:person.0643255040.16
175 rdf:rest Nc0d5c2cdb4c44c309221412e8c84bf46
176 N880aff6d85694093b309d3cd6fcf171a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Case-Control Studies
178 rdf:type schema:DefinedTerm
179 N961cf0c268534d74a6df31be4e41a3f6 schema:volumeNumber 42
180 rdf:type schema:PublicationVolume
181 N9d48ac37735b4ccaa4befb918fbe3d2b rdf:first sg:person.01164106722.99
182 rdf:rest N4f9da0321cd549a491b0880200ce2742
183 Na43114dabd884e019aabc610e68cfd08 rdf:first sg:person.01343321656.69
184 rdf:rest Nc810c2e5bd3e471b8665f36a5b314757
185 Naaba6f52702841688264096b218a1a14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name Insulin Receptor Substrate Proteins
187 rdf:type schema:DefinedTerm
188 Nac767c6db3a0439bb7331258388873dd schema:name pubmed_id
189 schema:value 29717275
190 rdf:type schema:PropertyValue
191 Naff3da5ebc904189a7cdccb19239dd06 schema:issueNumber 9
192 rdf:type schema:PublicationIssue
193 Nbe896a71c2824f1fb614b5c8cc55b826 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
194 schema:name Middle Aged
195 rdf:type schema:DefinedTerm
196 Nc0d5c2cdb4c44c309221412e8c84bf46 rdf:first sg:person.0704634134.00
197 rdf:rest Nd4a3706efad84225a54aeff3e61baacc
198 Nc810c2e5bd3e471b8665f36a5b314757 rdf:first sg:person.0722266435.55
199 rdf:rest Ndf1d54123a434f30aa197f5c5e8370a7
200 Ncb48840b3ff64230ac38a14c2a022ec3 rdf:first sg:person.0716766352.19
201 rdf:rest N7748f04eacbf4bb9a460c92ca80ace26
202 Nd18fdb55eb0f4a61b45510232eaa1378 rdf:first sg:person.0646631700.17
203 rdf:rest Nf22e7bbfd2a7423a929e7a50c8ab1fd9
204 Nd4107a58a67543f490fb365be52e5346 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
205 schema:name Liver
206 rdf:type schema:DefinedTerm
207 Nd4a3706efad84225a54aeff3e61baacc rdf:first sg:person.01264265721.56
208 rdf:rest N9d48ac37735b4ccaa4befb918fbe3d2b
209 Nd73a6643d8064b04ad9758ee6d0bab31 rdf:first sg:person.01101503716.31
210 rdf:rest rdf:nil
211 Ndf1d54123a434f30aa197f5c5e8370a7 rdf:first sg:person.01272145150.58
212 rdf:rest N5de17d7a94f64116b6d39db1260c1f47
213 Nea02339a80f2484e85889d81bc7d4bed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
214 schema:name Insulin Resistance
215 rdf:type schema:DefinedTerm
216 Nf22e7bbfd2a7423a929e7a50c8ab1fd9 rdf:first sg:person.0603136414.81
217 rdf:rest Ncb48840b3ff64230ac38a14c2a022ec3
218 Nfedd0fd5a0624cb5bc795476807b5df2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
219 schema:name Male
220 rdf:type schema:DefinedTerm
221 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
222 schema:name Medical and Health Sciences
223 rdf:type schema:DefinedTerm
224 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
225 schema:name Clinical Sciences
226 rdf:type schema:DefinedTerm
227 sg:grant.5909462 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
228 rdf:type schema:MonetaryGrant
229 sg:grant.5915768 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
230 rdf:type schema:MonetaryGrant
231 sg:grant.6112009 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
232 rdf:type schema:MonetaryGrant
233 sg:grant.6835318 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
234 rdf:type schema:MonetaryGrant
235 sg:grant.7522407 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
236 rdf:type schema:MonetaryGrant
237 sg:grant.7522408 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
238 rdf:type schema:MonetaryGrant
239 sg:grant.7543051 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
240 rdf:type schema:MonetaryGrant
241 sg:grant.9341932 http://pending.schema.org/fundedItem sg:pub.10.1038/s41366-018-0062-9
242 rdf:type schema:MonetaryGrant
243 sg:journal.1035838 schema:issn 0307-0565
244 1476-5497
245 schema:name International Journal of Obesity
246 schema:publisher Springer Nature
247 rdf:type schema:Periodical
248 sg:person.01030314210.81 schema:affiliation grid-institutes:grid.69566.3a
249 schema:familyName Izumi
250 schema:givenName Tomohito
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01030314210.81
252 rdf:type schema:Person
253 sg:person.010427522032.32 schema:affiliation grid-institutes:grid.480536.c
254 schema:familyName Ueno
255 schema:givenName Yoshiyuki
256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010427522032.32
257 rdf:type schema:Person
258 sg:person.01101503716.31 schema:affiliation grid-institutes:grid.69566.3a
259 schema:familyName Katagiri
260 schema:givenName Hideki
261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101503716.31
262 rdf:type schema:Person
263 sg:person.01142407026.96 schema:affiliation grid-institutes:grid.69566.3a
264 schema:familyName Murakami
265 schema:givenName Keigo
266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142407026.96
267 rdf:type schema:Person
268 sg:person.01164106722.99 schema:affiliation grid-institutes:grid.268394.2
269 schema:familyName Mizuno
270 schema:givenName Kei
271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01164106722.99
272 rdf:type schema:Person
273 sg:person.01255535707.76 schema:affiliation grid-institutes:grid.69566.3a
274 schema:familyName Shimosegawa
275 schema:givenName Tooru
276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255535707.76
277 rdf:type schema:Person
278 sg:person.01264265721.56 schema:affiliation grid-institutes:grid.69566.3a
279 schema:familyName Kondo
280 schema:givenName Yasuteru
281 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264265721.56
282 rdf:type schema:Person
283 sg:person.01264270414.13 schema:affiliation grid-institutes:grid.69566.3a
284 schema:familyName Sawada
285 schema:givenName Shojiro
286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264270414.13
287 rdf:type schema:Person
288 sg:person.01272145150.58 schema:affiliation grid-institutes:grid.69566.3a
289 schema:familyName Kodama
290 schema:givenName Shinjiro
291 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272145150.58
292 rdf:type schema:Person
293 sg:person.01343321656.69 schema:affiliation grid-institutes:grid.69566.3a
294 schema:familyName Yamada
295 schema:givenName Tetsuya
296 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01343321656.69
297 rdf:type schema:Person
298 sg:person.01345464520.60 schema:affiliation grid-institutes:grid.412757.2
299 schema:familyName Kawagishi
300 schema:givenName Naoki
301 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01345464520.60
302 rdf:type schema:Person
303 sg:person.015433216133.49 schema:affiliation grid-institutes:grid.69566.3a
304 schema:familyName Honma
305 schema:givenName Midori
306 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015433216133.49
307 rdf:type schema:Person
308 sg:person.0603136414.81 schema:affiliation grid-institutes:grid.69566.3a
309 schema:familyName Tsukita
310 schema:givenName Sohei
311 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0603136414.81
312 rdf:type schema:Person
313 sg:person.0643255040.16 schema:familyName Imai
314 schema:givenName Junta
315 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0643255040.16
316 rdf:type schema:Person
317 sg:person.0646631700.17 schema:affiliation grid-institutes:grid.69566.3a
318 schema:familyName Takahashi
319 schema:givenName Kei
320 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646631700.17
321 rdf:type schema:Person
322 sg:person.0704634134.00 schema:affiliation grid-institutes:grid.69566.3a
323 schema:familyName Kakazu
324 schema:givenName Eiji
325 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0704634134.00
326 rdf:type schema:Person
327 sg:person.0716766352.19 schema:familyName Uno
328 schema:givenName Kenji
329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716766352.19
330 rdf:type schema:Person
331 sg:person.0722266435.55 schema:affiliation grid-institutes:grid.69566.3a
332 schema:familyName Gao
333 schema:givenName Junhong
334 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722266435.55
335 rdf:type schema:Person
336 sg:pub.10.1007/s00018-008-8322-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029759544
337 https://doi.org/10.1007/s00018-008-8322-9
338 rdf:type schema:CreativeWork
339 sg:pub.10.1007/s11892-009-0034-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011237758
340 https://doi.org/10.1007/s11892-009-0034-5
341 rdf:type schema:CreativeWork
342 sg:pub.10.1007/s12038-010-0052-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025296298
343 https://doi.org/10.1007/s12038-010-0052-0
344 rdf:type schema:CreativeWork
345 sg:pub.10.1038/414799a schema:sameAs https://app.dimensions.ai/details/publication/pub.1000331422
346 https://doi.org/10.1038/414799a
347 rdf:type schema:CreativeWork
348 sg:pub.10.1038/hr.2013.80 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041803518
349 https://doi.org/10.1038/hr.2013.80
350 rdf:type schema:CreativeWork
351 sg:pub.10.1038/hr.2014.20 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044401479
352 https://doi.org/10.1038/hr.2014.20
353 rdf:type schema:CreativeWork
354 sg:pub.10.1038/ijo.2012.181 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009999572
355 https://doi.org/10.1038/ijo.2012.181
356 rdf:type schema:CreativeWork
357 sg:pub.10.1038/ncomms12977 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036117907
358 https://doi.org/10.1038/ncomms12977
359 rdf:type schema:CreativeWork
360 sg:pub.10.1038/nm1662 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039117182
361 https://doi.org/10.1038/nm1662
362 rdf:type schema:CreativeWork
363 sg:pub.10.1038/nrm4074 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020513835
364 https://doi.org/10.1038/nrm4074
365 rdf:type schema:CreativeWork
366 sg:pub.10.1111/j.1572-0241.1999.01377.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015032643
367 https://doi.org/10.1111/j.1572-0241.1999.01377.x
368 rdf:type schema:CreativeWork
369 grid-institutes:grid.268394.2 schema:alternateName Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
370 schema:name Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
371 rdf:type schema:Organization
372 grid-institutes:grid.412757.2 schema:alternateName Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan
373 schema:name Division of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Sendai, Japan
374 rdf:type schema:Organization
375 grid-institutes:grid.480536.c schema:alternateName Japan Agency for Medical Research and Development, CREST, Tokyo, Japan
376 schema:name Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
377 Japan Agency for Medical Research and Development, CREST, Tokyo, Japan
378 rdf:type schema:Organization
379 grid-institutes:grid.69566.3a schema:alternateName Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan
380 Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan
381 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
382 Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
383 schema:name Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan
384 Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan
385 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
386 Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
387 Japan Agency for Medical Research and Development, CREST, Tokyo, Japan
388 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...