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Author Notes:

Address for Correspondence: Mailing Address: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 315 Ferst Dr. NW, IBB Building-Room 1306 Atlanta, GA 30332 athanassios.sambanis@chbe.gatech.edu Telephone Number: (404) 894-2869 Fax Number: (404) 894-2291

We gratefully acknowledge José Vasquez and Derrius Anderson (Undergraduate Research Assistants, GT) for their assistance in the PCR and HDACi studies, and Drs. Brubaker and Drucker (University of Toronto Ontario, Canada) for their donation of the GLUTag cells.

Subjects:

Research Funding:

We gratefully acknowledge our funding source NIH (R01 DK076801)

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • Histone deacetylase inhibitors
  • Trichostatin A
  • Regulated secretory pathway
  • Diabetes
  • beta-cells
  • Intestinal endocrine cells
  • HISTONE DEACETYLASE INHIBITORS
  • GLUCAGON-LIKE PEPTIDE-1
  • INSULIN-SECRETION
  • ACETYLATION
  • GENE
  • TRANSCRIPTION
  • REACTIVATION
  • ACTIVATION
  • MECHANISMS
  • EXPRESSION

Trichostatin A affects the secretion pathways of beta and intestinal endocrine cells

Tools:

Journal Title:

Experimental Cell Research

Volume:

Volume 330, Number 1

Publisher:

, Pages 212-221

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Histone deacetylase inhibitors (HDACi) were recently identified as having significant clinical potential in reversing β-cell functional inhibition caused by inflammation, a shared precursor of Type 1 and Type 2 diabetes. However, HDACi are highly complex and little is known of their direct effect on important cell secretion pathways for blood glucose regulation. The aims of the present study were to investigate the effect of HDACi on insulin secretion from β-cells, GLP-1 secretion from L-cells, and recombinant insulin secretion from engineered L-cells. The β-cell line βTC-tet, L-cell line GLUTag, or recombinant insulin-secreting L-cell lines were exposed to Trichostatin A for 24. h. Effects on insulin or GLP-1 mRNA, intracellular protein content, processing efficiency, and secretion were measured by real-time PCR, ELISA, and radioimmunoassay. HDACi increased secretion per viable cell in a dose-dependent manner for all cell types. Effects on mRNA levels were variable, but enhanced intracellular polypeptide content and secretion were comparable among cell types. Enhanced recombinant insulin secretion was sustained for seven days in alginate microencapsulated L-cells. HDACi enhances β- and L-cell secretion fluxes in a way that could significantly improve blood glucose regulation in diabetes patients and holds potential as a novel method for enhancing insulin-secreting non-β or β-cell grafts.

Copyright information:

© 2014 Elsevier Inc.

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