http://www.cnr.it/ontology/cnr/individuo/prodotto/ID193387

Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease (Articolo in rivista) (literal)

Anno

2012-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1002/hep.24793 (literal)

Alternative label

Bechmann, L.P.;Gastaldelli, A.;Vetter, D.;Patman, G.L.;Pascoe, L.;Hannivoort, R.A.;Lee, U.E.;Fiel, I.;Munoz, U.;Ciociaro, D.;Lee, Y.M.;Buzzigoli, E.;Miele, L.;Hui, K.Y.;Bugianesi, E.;Burt, A.D.;Day, C.P.;Mari, A.;Agius, L.;Walker, M.;Friedman, S.L.;Reeves, H.L. (2012)
Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease
in Hepatology (Baltim. Md. : Online); J. Wiley & sons, New York (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Bechmann, L.P.;Gastaldelli, A.;Vetter, D.;Patman, G.L.;Pascoe, L.;Hannivoort, R.A.;Lee, U.E.;Fiel, I.;Munoz, U.;Ciociaro, D.;Lee, Y.M.;Buzzigoli, E.;Miele, L.;Hui, K.Y.;Bugianesi, E.;Burt, A.D.;Day, C.P.;Mari, A.;Agius, L.;Walker, M.;Friedman, S.L.;Reeves, H.L. (literal)

Pagina inizio

1083 (literal)

Pagina fine

1093 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://onlinelibrary.wiley.com/doi/10.1002/hep.24793/abstract (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

55 (literal)

Rivista

Hepatology (Rivista)

Note

ISI Web of Science (WOS) (literal)
Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Bechmann: Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY / Department of Gastroenterology and Hepatology, University Hospital Essen, Germany; Gastaldelli, Ciociar, Buzzigali: Institute of Clinical Physiology, National Research Council, Pisa, Italy / RISC Consortium, Pisa, Italy; Vetter, Lee, Munoz, Lee, Friedman: Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, United States; Patman, Hui: Northern Institute for Cancer Research, Newcastle University, United Kingdom; Pascoe: RISC Consortium, Pisa, Italy / Institute of Cellular Medicine, Newcastle University, United Kingdom; Hannivoort: Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, United States / Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Fiel: Department of Pathology, Mount Sinai School of Medicine, New York, NY, United States; Miele: Northern Institute for Cancer Research, Newcastle University, United Kingdom / Department of Internal Medicine, Policlinico Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy; Bugianesi: Department of Gastroenterology, University of Turin, Italy; Burt, Day, Agius: Institute of Cellular Medicine, Newcastle University, United Kingdom; Mari: RISC Consortium, Pisa, Italy / Institute of Biomedical Engineering, National Research Council, Padua, Italy; Walker: RISC Consortium, Pisa, Italy / Institute of Cellular Medicine, Newcastle University, United Kingdom; Reeves: Northern Institute for Cancer Research, Newcastle University, United Kingdom / Hepatopancreatobiliary Group, Freeman Hospital, Newcastle-upon-Tyne, United Kingdom (literal)

Titolo

Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease (literal)

Abstract

he polymorphism, KLF6-IVS1-27A, in the Kruppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of nonalcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development of insulin resistance, central to NAFLD pathogenesis, we genotyped KLF6-IVS1-27 in healthy subjects and assayed fasting plasma glucose (FPG) and insulin sensitivities. Furthermore, we quantified messenger RNA (mRNA) expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, in human livers and in liver tissues derived from a murine Klf6 knockdown model (DeltaKlf6). Klf6 overexpression studies in a mouse hepatocyte line were utilized to mechanistically link KLF6 with Gck promoter activity. KLF6-IVS1-27Gwt (i.e., less KLF6 splicing) was associated with stepwise increases in FPG and insulin and reduced hepatic insulin sensitivity. KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target. Accordingly, in DeltaKlf6 hepatocytes Gck expression was reduced and stable transfection of Klf6 led to up-regulation of Gck. GCK and KLF6 mRNAs correlate directly in human NAFLD tissues and immunohistochemistry studies confirm falling levels of both KLF6 and GCK in fat-laden hepatocytes. In contrast to full-length KLF6, splice variant KLF6-SV1 increases in NAFLD hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity. Conclusion: KLF6 regulation of GCK contributes to the development of hepatic insulin resistance. The KLF6-IVS1-27A polymorphism, which generates more KLF6-SV1, combats this, lowering hepatic insulin resistance and blood glucose (literal)

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