Differential expression of regulators of the canonical Wnt pathway during the compensatory beta-cell hyperplasia in prediabetic mice

Author(s)

Maschio, Daniela Aparecida ; Pinto Hernandes, Leticia Helena ; Alvares, Lucia Elvira ; Marques-Souza, Henrique ; Collares-Buzato, Carla Beatriz

• Document type: Journal article
• Source: Biochemical and Biophysical Research Communications; v. 611, p. 7-pg., 2022-04-28.

Abstract

We previously reported that the canonical Wnt signaling pathway is activated during compensatory islet hyperplasia in prediabetic mice. Here, we aimed to expand our knowledge concerning the Wnt signaling partners and modulators involved in this process. We report here that Axin1, Axin2, and DACT1, inhibitors of the canonical Wnt signaling pathway, displayed no change in their expression, while GSK-3 beta, a multi-functional kinase that acts as a negative regulator of this pathway as well as affects insulin secretion/action, was up-regulated in hyperplastic islets of prediabetic mice. We also observed that COUP-TFII, a protein that acts positively on Wnt-target genes related to cell proliferation, displays a significant increase in gene expression and protein content and is highly immunolabeled in islet cell nuclei of prediabetic mice compared to control islets. These findings suggest that GSK-3b and COUP-TFII may play a role in beta-cell dysfunction and hyperplasia during type 2 prediabetes. (C) 2022 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 15/25442-1 - Role of the canonical and non-canonical Wnt signaling pathway in the beta cell function and proliferation during experimental prediabetes
• Grantee: Carla Beatriz Collares Buzato
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/09602-0 - Characterization of the gene regulatory network controled by Coup-TFII in cardiomyocytes derived from embryonic stem cells
• Grantee: Henrique Marques Barbosa de Souza
• Support Opportunities: Research Grants - Young Investigators Grants