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PIMT regulates hepatic gluconeogenesis in mice.
Kapadia, Bandish; Behera, Soma; Kumar, Sireesh T; Shah, Tapan; Edwin, Rebecca Kristina; Babu, Phanithi Prakash; Chakrabarti, Partha; Parsa, Kishore V L; Misra, Parimal.
Afiliación
  • Kapadia B; Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
  • Behera S; Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
  • Kumar ST; Department of Biotechnology, University of Hyderabad, Hyderabad 500046, India.
  • Shah T; Department of Biochemistry, Saurashtra University, Rajkot 360005, India.
  • Edwin RK; Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
  • Babu PP; Department of Biotechnology, University of Hyderabad, Hyderabad 500046, India.
  • Chakrabarti P; Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India.
  • Parsa KVL; Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
  • Misra P; Center for Innovation in Molecular and Pharmaceutical Sciences, Dr. Reddy's Institute of Life Sciences (DRILS), University of Hyderabad Campus, Hyderabad, TG 500046, India.
iScience ; 26(3): 106120, 2023 Mar 17.
Article en En | MEDLINE | ID: mdl-36866247
The physiological and metabolic functions of PIMT/TGS1, a third-generation transcriptional apparatus protein, in glucose homeostasis sustenance are unclear. Here, we observed that the expression of PIMT was upregulated in the livers of short-term fasted and obese mice. Lentiviruses expressing Tgs1-specific shRNA or cDNA were injected into wild-type mice. Gene expression, hepatic glucose output, glucose tolerance, and insulin sensitivity were evaluated in mice and primary hepatocytes. Genetic modulation of PIMT exerted a direct positive impact on the gluconeogenic gene expression program and hepatic glucose output. Molecular studies utilizing cultured cells, in vivo models, genetic manipulation, and PKA pharmacological inhibition establish that PKA regulates PIMT at post-transcriptional/translational and post-translational levels. PKA enhanced 3'UTR-mediated translation of TGS1 mRNA and phosphorylated PIMT at Ser656, increasing Ep300-mediated gluconeogenic transcriptional activity. The PKA-PIMT-Ep300 signaling module and associated PIMT regulation may serve as a key driver of gluconeogenesis, positioning PIMT as a critical hepatic glucose sensor.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos