Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity

JCI Insight. 2023 Aug 22;8(16):e166386. doi: 10.1172/jci.insight.166386.


Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet β cells, characterized by inappropriate production of other islet cell-enriched hormones. Here, we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin+ (Gast+) cells generated under conditions of chronic hyperglycemia and obesity. A human β cell line deficient in MAFB, but not one lacking MAFA, also produced a GAST+ gene expression pattern. In addition, GAST was detected in human T2D β cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repress GAST gene transcription. These results support a potentially novel, species-specific role for MafA and MAFB in maintaining adult mouse and human β cell identity, respectively. Here, we discuss the possibility that induction of Gast/GAST and other non-β cell hormones, by reduction in the levels of these transcription factors, represents a dysfunctional β cell signature.

Keywords: Beta cells; Cell Biology; Diabetes; Endocrinology; Islet cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Diabetes Mellitus, Type 2*
  • Humans
  • Insulin
  • Insulin-Secreting Cells*
  • Islets of Langerhans*
  • MafB Transcription Factor / genetics
  • Mice


  • MafB Transcription Factor
  • Insulin
  • MAFB protein, human