Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism

World Journal of Biological Chemistry
Anke Hoffmann, Dietmar Spengler

Abstract

Transient neonatal diabetes mellitus 1 (TNDM1) is a rare genetic disorder representing with severe neonatal hyperglycaemia followed by remission within one and a half year and adolescent relapse with type 2 diabetes in half of the patients. Genetic defects in TNDM1 comprise uniparental isodisomy of chromosome 6, duplication of the minimal TNDM1 locus at 6q24, or relaxation of genomically imprinted ZAC1/HYMAI. Whereas the function of HYMAI, a non-coding mRNA, is still unidentified, biochemical and molecular studies show that zinc finger protein 1 regulating apoptosis and cell cycle arrest (ZAC1) behaves as a factor with versatile transcriptional functions dependent on binding to specific GC-rich DNA motives and interconnected regulation of recruited coactivator activities. Genome-wide expression profiling enabled the isolation of a number of Zac1 target genes known to regulate different aspects of β-cell function and peripheral insulin sensitivity. Among these, upregulation of Pparγ and Tcf4 impairs insulin-secretion and β-cell proliferation. Similarly, Zac1-mediated upregulation of Socs3 may attenuate β-cell proliferation and survival by inhibition of growth factor signalling. Additionally, Zac1 directly represses Pac1 and Rasg...Continue Reading

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Citations

Jul 28, 2016·Journal of Veterinary Internal Medicine·C GilorS P DiBartola
Oct 20, 2017·Diabetic Medicine : a Journal of the British Diabetic Association·B Y CaoX Q Li
Aug 3, 2017·Neonatal Network : NN·Martha Anne ZammitJean Calleja-Agius
Mar 11, 2017·Journal of Assisted Reproduction and Genetics·Amr Rafat Elhamamsy
Apr 18, 2018·Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology·Tohru YorifujiRie Kawakita
Oct 4, 2018·Current Diabetes Reports·Haichen Zhang, Toni I Pollin
Nov 12, 2020·International Journal of Molecular Sciences·Rebekah R StarksGeetu Tuteja

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