Wnt4 antagonises Wnt3a mediated increases in growth and glucose stimulated insulin secretion in the pancreatic beta-cell line, INS-1

Bowen, Angela; Kos, Katarina; Whatmore, Jacqueline L.; Richardson, Sarah J.; Welters, Hannah J.

doi:10.1016/j.bbrc.2016.09.130

Cited by 13 publications

(16 citation statements)

References 29 publications

(43 reference statements)

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“…Therefore, upregulation of Wnt4 expression may be associated with compensatory enhancement of the insulin secretory response, but not insulin biosynthesis, in diet-induced insulin-resistant mice. In line with former reports [12,23], the addition of exogenous WNT4 did not exert a notable effect on insulin secretion. Although its precise mechanisms remain unknown, it is feasible that WNT4 is secreted from β-cells and acts as a ligand for its receptor in an autocrine/paracrine manner, thereby prohibiting additional ligand binding.…”

Section: Discussionsupporting

confidence: 92%

“…However, the precise role of Wnt4 in diabetes and insulin resistance has not yet been elucidated. In pancreatic islets and INS-1 cells, WNT4 inhibits WNT3a-mediated increases in proliferation and glucose-stimulated insulin secretion [12]. The abundance of WNT4 in pancreatic islets and its increase in response to insulin resistance implies potential roles of WNT4 in pancreatic islets independent of WNT3a.…”

Section: Discussionmentioning

confidence: 99%

“…Wnt4 knockdown resulted in no significant difference in the number of viable cells, suggesting that WNT4 does not affect the regulation of MIN6 cell proliferation. In rat INS-1 cells, the role of endogenous WNT4 in cell proliferation has been controversial [12,23]. Overall, the role of endogenously expressed WNT4 may vary depending on the cell type.…”

Section: Discussionmentioning

confidence: 99%

“…The addition of purified WNT3a protein to cultured β-cells or islets promotes expression of Pitx2, a direct target of WNT signaling, as well as Cyclin D2, an essential regulator of the β-cell cycle and proliferation [11]. WNT4 completely blocks WNT3a-stimulated β-cell growth and insulin secretion [12]. In the present study, we examined the putative relevance of WNT4 signaling to the pathogenesis of diabetes and insulin resistance under a HF/HS diet in mice.…”

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confidence: 98%

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A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

et al. 2018

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

et al. 2018

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“…Conversely, incubating cells with the GSK3 inhibitor BIO increases β-catenin levels and as a result of that, GSIS was also increased [ 42 ]. Other groups have shown that insulin secretion is increased by treatment of β-cells with Wnts, which will also increase β-catenin [ 43 , 44 ]. The in vivo data on the role of β-catenin in insulin secretion are more difficult to interpret given that this is largely based on knockout models as long term loss of β-catenin has multiple effects on cell function and differentiation state.…”

Section: The Role Of Catenin’s In the Regulation Of Insulin Secretionmentioning

confidence: 99%

The role of adherens junction proteins in the regulation of insulin secretion

2018

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In healthy individuals, any rise in blood glucose levels is rapidly countered by the release of insulin from the β-cells of the pancreas which in turn promotes the uptake and storage of the glucose in peripheral tissues. The β-cells possess exquisite mechanisms regulating the secretion of insulin to ensure that the correct amount of insulin is released. These mechanisms involve tight control of the movement of insulin containing secretory vesicles within the β-cells, initially preventing most vesicles being able to move to the plasma membrane. Elevated glucose levels trigger an influx of Ca2+ that allows fusion of the small number of insulin containing vesicles that are pre-docked at the plasma membrane but glucose also stimulates processes that allow other insulin containing vesicles located further in the cell to move to and fuse with the plasma membrane. The mechanisms controlling these processes are complex and not fully understood but it is clear that the interaction of the β-cells with other β-cells in the islets is very important for their ability to develop the appropriate machinery for proper regulation of insulin secretion. Emerging evidence indicates one factor that is key for this is the formation of homotypic cadherin mediated adherens junctions between β-cells. Here, we review the evidence for this and discuss the mechanisms by which these adherens junctions might regulate insulin vesicle trafficking as well as the implications this has for understanding the dysregulation of insulin secretion seen in pathogenic states.

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Islet cells are the source of Wnts that can induce beta‐cell proliferation in vitro

Maschio

Matheus

Collares-Buzato

2019

Journal Cellular Physiology

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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 betacell 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.

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Wnt4 antagonises Wnt3a mediated increases in growth and glucose stimulated insulin secretion in the pancreatic beta-cell line, INS-1

Cited by 13 publications

References 29 publications

A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

A High-Fat/High-Sucrose Diet Induces WNT4 Expression in Mouse Pancreatic β-cells

The role of adherens junction proteins in the regulation of insulin secretion

Islet cells are the source of Wnts that can induce beta‐cell proliferation in vitro

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