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Islet cells are the source of Wnts that can induce beta‐cell proliferation in vitro
Author(s) -
Maschio Daniela A.,
Matheus Valquíria A.,
CollaresBuzato Carla B.
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28584
Subject(s) - wnt signaling pathway , islet , pancreas , endocrinology , biology , medicine , beta cell , microbiology and biotechnology , paracrine signalling , cell growth , secretion , insulin , signal transduction , biochemistry , receptor
Wnt proteins act mainly as paracrine signals regulating cell proliferation and differentiation. The canonical Wnt pathway has recently been associated with pancreas development and the onset of type 2 diabetes in rodent and human but the underlying mechanisms are still unclear. The aim of this work was threefold: (a) to screen for Wnt expressed by murine pancreas/islet cells, (b) to investigate whether the Wnt gene expression profile can be changed in hyperplastic islets from type 2 prediabetic mice (fed a high‐fat diet), and (c) to verify whether soluble factors (namely Wnts) released by pancreatic islets affect insulin secretion and proliferation of a beta‐cell line in vitro condition. The majority of the Wnt subtypes are expressed by islet cells, such as Wnts 2, 2b, 3, 3a, 4, 5a, 5b, 6, 7a, 7b, 8a, 8b, 9a, 9b, and 11, while in the whole pancreas homogenates were found the same subtypes, except Wnts 3, 6, 7a, and 7b. Among all the Wnts, the Wnts 3a and 5b showed a significantly increased gene expression in hyperplastic islets from prediabetic mice compared with those from control mice. Furthermore, we observed that coculture with hyperplastic or nonhyperplastic islets did not change the secretory function of the mouse insulinoma clone 6 (MIN6) beta cells but induced a significant increase in cell proliferation in this lineage, which was partially blocked by the IWR‐1 and IWP‐2 Wnt inhibitors. In conclusion, we demonstrated that murine pancreas/islet cells can secrete Wnts, and that islet‐released Wnts may participate in the regulation of beta‐cell mass under normal and prediabetic conditions.