MafA expression and insulin promoter activity are induced by nicotinamide and related compounds in INS-1 pancreatic beta-cells

Diabetes
Diana Z YeL Karl Olson

Abstract

Nicotinamide has been reported to induce differentiation of precursor/stem cells toward a beta-cell phenotype, increase islet regeneration, and enhance insulin biosynthesis. Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity. The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose. In contrast, the potent PARP-1 inhibitors PJ34 or INO-1001 had no effect on promoter activity. Antioxidants, including N-acetylcysteine, lipoic acid, or quercetin, only minimally induced the insulin promoter. Site-directed mutations of the human insulin promoter mapped the low-potency PARP inhibitor response to the C1 element, which serves as a MafA binding site. INS-1 cells exposed to elevated glucose had markedly reduced MafA protein and mRNA levels. Low-potency PARP inhibitors restored MafA mRNA and protein...Continue Reading

References

Jun 1, 1992·Journal of Epidemiology and Community Health·D P Strachan
Sep 1, 1993·The Journal of Clinical Investigation·T OtonkoskiA Hayek
May 1, 1997·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Sander, M S German
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y TanakaR P Robertson
Feb 5, 2000·Redox Report : Communications in Free Radical Research·J P Kamat, T P Devasagayam
Jun 1, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·A H BoularesS D Cohen
Feb 13, 2001·Biochemical and Biophysical Research Communications·T SuzukiD R Crawford
Jun 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·O UllrichR Nitsch
Aug 21, 2001·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·F G SorianoC Szabó
Jan 10, 2002·The Journal of Biological Chemistry·D Ross LaybuttGordon C Weir
May 16, 2002·The Journal of Biological Chemistry·Hideaki KanetoGordon C Weir
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Martin OlbrotArun Sharma
Sep 26, 2002·The Journal of Biological Chemistry·Kevin J BittermanDavid A Sinclair
Oct 9, 2002·The Journal of Biological Chemistry·Kohsuke KataokaHiroshi Handa
Jun 18, 2003·Cell·W Lee Kraus, John T Lis
Aug 15, 2003·Molecular and Cellular Biology·Taka-aki MatsuokaRoland Stein
Sep 13, 2005·Cell Metabolism·Yukari Ido KitamuraDomenico Accili

❮ Previous
Next ❯

Citations

Jan 30, 2013·Molecular Aspects of Medicine·Carles CantóPeter Bai
Nov 26, 2008·The Journal of Biological Chemistry·Chunli Shao, Melanie H Cobb
Jul 31, 2009·Experimental & Molecular Medicine·Da-Yeon JungSung-Joo Kim
Jan 23, 2016·Cell and Tissue Research·Pengcheng ZhouZhiwei Wang
Nov 14, 2012·Journal of Tissue Engineering and Regenerative Medicine·So Young ChunShay Soker
Jan 9, 2008·Molecular Immunology·Katie LoniewskiNarayanan Parameswaran
Jun 3, 2017·International Journal of Molecular Sciences·Ángeles OrtegaBernat Soria
Nov 26, 2014·Nutrients·Genoveva BernáFranz Martín
Feb 23, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Esraa M ZakariaHany M El-Bassossy
Jan 27, 2011·American Journal of Physiology. Endocrinology and Metabolism·Christopher D Green, L Karl Olson
Jul 25, 2021·Clinical Epigenetics·Amitava Basu, Vijay K Tiwari
Aug 28, 2021·Progress in Lipid Research·Magdolna SzántóPeter Bai

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Antidiabetic Cellular Plasticity

This feed focuses on mechanisms that underlie cellular plasticity as a treatment for diabetes and other degenerative diseases.

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.