» Articles » PMID: 35562869

Role of the Transcription Factor MAFA in the Maintenance of Pancreatic β-Cells

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 May 14
PMID 35562869
Authors
Affiliations
Soon will be listed here.
Abstract

Pancreatic β-cells are specialized to properly regulate blood glucose. Maintenance of the mature β-cell phenotype is critical for glucose metabolism, and β-cell failure results in diabetes mellitus. Recent studies provide strong evidence that the mature phenotype of β-cells is maintained by several transcription factors. These factors are also required for β-cell differentiation from endocrine precursors or maturation from immature β-cells during pancreatic development. Because the reduction or loss of these factors leads to β-cell failure and diabetes, inducing the upregulation or inhibiting downregulation of these transcription factors would be beneficial for studies in both diabetes and stem cell biology. Here, we discuss one such factor, i.e., the transcription factor MAFA. MAFA is a basic leucine zipper family transcription factor that can activate the expression of insulin in β-cells with PDX1 and NEUROD1. MAFA is indeed indispensable for the maintenance of not only insulin expression but also function of adult β-cells. With loss of MAFA in type 2 diabetes, β-cells cannot maintain their mature phenotype and are dedifferentiated. In this review, we first briefly summarize the functional roles of MAFA in β-cells and then mainly focus on the molecular mechanism of cell fate conversion regulated by MAFA.

Citing Articles

A stepwise approach to deriving functional β-cells from human embryonic or induced pluripotent stem cells.

Farhat C, Xega V, Liu J Med Rev (2021). 2025; 5(1):23-34.

PMID: 39974557 PMC: 11834748. DOI: 10.1515/mr-2024-0039.


Reformed islets: a long-term primary cell platform for exploring mouse and human islet biology.

Haq N, Toczyska K, Wilson M, Jacobs M, Zhao M, Lei Y Cell Death Discov. 2024; 10(1):480.

PMID: 39580467 PMC: 11585622. DOI: 10.1038/s41420-024-02234-6.


Enhanced BMP Signaling Alters Human β-Cell Identity and Function.

Dekker E, Trinanes J, Munoz Garcia A, de Graaf N, de Koning E, Carlotti F Adv Biol (Weinh). 2024; 9(1):e2400470.

PMID: 39499224 PMC: 11760635. DOI: 10.1002/adbi.202400470.


Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.

Sokolowski E, Kursawe R, Selvam V, Bhuiyan R, Thibodeau A, Zhao C Cell Metab. 2024; 36(11):2468-2488.e7.

PMID: 39383866 PMC: 11798411. DOI: 10.1016/j.cmet.2024.09.006.


Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.

Gojani E, Rai S, Norouzkhani F, Shujat S, Wang B, Li D Curr Issues Mol Biol. 2024; 46(7):7621-7667.

PMID: 39057094 PMC: 11275945. DOI: 10.3390/cimb46070453.


References
1.
Aguayo-Mazzucato C, Koh A, El Khattabi I, Li W, Toschi E, Jermendy A . Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia. 2010; 54(3):583-93. PMC: 3047400. DOI: 10.1007/s00125-010-2026-z. View

2.
Trinanes J, Ten Dijke P, Groen N, Hanegraaf M, Porrini E, Rodriguez-Rodriguez A . Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger β-Cell Failure. Diabetes. 2019; 69(2):193-204. DOI: 10.2337/db19-0828. View

3.
Okauchi S, Shimoda M, Obata A, Kimura T, Hirukawa H, Kohara K . Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic β-cells in obese type 2 diabetic db/db mice. Biochem Biophys Res Commun. 2015; 470(3):772-782. DOI: 10.1016/j.bbrc.2015.10.109. View

4.
Ni Q, Gu Y, Xie Y, Yin Q, Zhang H, Nie A . Raptor regulates functional maturation of murine beta cells. Nat Commun. 2017; 8:15755. PMC: 5472774. DOI: 10.1038/ncomms15755. View

5.
Cyphert H, Walker E, Hang Y, Dhawan S, Haliyur R, Bonatakis L . Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally. Diabetes. 2018; 68(2):337-348. PMC: 6341297. DOI: 10.2337/db18-0903. View