Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.10.20.512880v1?rss=1

Authors: Cha, J., Tong, X., Walker, E. M., Dahan, T., Cochrane, V., Ashe, S., Russell, R., Osipovich, A. B., Mawla, A. M., Guo, M., Liu, J.-h., Huising, M. O., Magnuson, M. A., Hebrok, M., Dor, Y., Stein, R.

Abstract:
Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet beta ({beta}) 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 {beta} cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin (Gast)-positive cells generated under conditions of chronic hyperglycemia and obesity. A human {beta} cell line deficient in MAFB, but not one lacking MAFA, also produced a gastrin (GAST)-positive gene expression pattern. In addition, GAST was detected in human T2D {beta} cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repress GAST gene transcription. These results support a novel, species-specific role for MafA and MAFB in maintaining adult mouse and human {beta} cell identity, respectively, by repressing expression of Gast/GAST and other non-{beta} cell hormones.

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