Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

Research output: Contribution to journalReview article

Authors

External Institution(s)

  • Case Western Reserve University
  • Sun Yat-Sen University

Details

Original languageEnglish (US)
Pages (from-to)R73-R85
JournalJournal of molecular endocrinology
Volume58
Issue number2
StatusPublished - Feb 1 2017
Peer-reviewedYes

Abstract

GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations. GLIS3 cooperates with pancreatic and duodenal homeobox 1 (PDX1), v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA), as well as neurogenic differentiation 1 (NEUROD1) and potently controls insulin gene transcription. GLIS3 also plays a role in β cell survival and likely in insulin secretion. Any perturbation of these functions may underlie all three forms of diabetes. GLIS3, synergistically with hepatocyte nuclear factor 6 (HNF6) and forkhead box A2 (FOXA2), controls fetal islet differentiation via transactivating neurogenin 3 (NGN3) and impairment of this function leads to neonatal diabetes. In addition, GLIS3 is also required for the compensatory β cell proliferation and mass expansion in response to insulin resistance, which if disrupted may predispose to T2D. The increasing understanding of the mechanisms of GLIS3 in β cell development, survival and function maintenance will provide new insights into disease pathogenesis and potential therapeutic target identification to combat diabetes.

    Research areas

  • GLIS3, Insulin, NGN3, Neonatal diabetes, Type 1 diabetes, Type 2 diabetes

Citation formats

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Wen, X & Yang, Y 2017, 'Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes', Journal of molecular endocrinology, vol. 58, no. 2, pp. R73-R85. https://doi.org/10.1530/JME-16-0232