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

• Type of Material: Article
• Authors: Aubrey R Tiernan, Georgia Institute of Technology; Julie A Champion, Georgia Institute of Technology; Athanassios Sambanis, Emory University
• Language: English
• Date: 2014-10-16
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yexcr.2014.09.031
• Title of Journal or Parent Work: Experimental Cell Research
• ISSN: 0014-4827
• Volume: 330
• Issue: 1
• Start Page: 212
• End Page: 221
• Grant/Funding Information: We gratefully acknowledge our funding source NIH (R01 DK076801)
• Keywords: Science & Technology; Trichostatin A; Cell Biology; Diabetes; GENE; Life Sciences & Biomedicine; HISTONE DEACETYLASE INHIBITORS; beta-cells; Intestinal endocrine cells; MECHANISMS; INSULIN-SECRETION; REACTIVATION; GLUCAGON-LIKE PEPTIDE-1; Regulated secretory pathway; Oncology; Histone deacetylase inhibitors; TRANSCRIPTION; ACETYLATION; ACTIVATION; EXPRESSION
• Research Categories: Biology, Molecular; Biology, Cell; Engineering, Biomedical

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.