Wnt4 antagonises Wnt3a mediated increases in growth and glucose stimulated insulin secretion in the pancreatic beta-cell line, INS-1.
The Wnt signalling pathway in beta-cells has been linked to the development of type 2 diabetes. Investigating the impact of a non-canonical Wnt ligand, Wnt4, on beta-cell function we found that in INS-1 cells, Wnt4 was able to completely block Wnt3a stimulated cell growth and insulin secretion. However, despite high levels of Wnt4 protein being detected in INS-1 cells, reducing the expression of Wnt4 had no impact on cell growth or Wnt3a signalling. As such, the role of the endogenously expressed Wnt4 in beta-cells is unclear, but the data showing that Wnt4 can act as a negative regulator of canonical Wnt signalling in beta-cells suggests that this pathway could be a potential target for modulating beta-cell function.
Institute of Biomedical & Clinical Science, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
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Bowen
Institute of Biomedical & Clinical Science, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
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Kos
Institute of Biomedical & Clinical Science, University of Exeter Medical School, St Luke's Campus, Heavitree Road, Exeter EX1 2LU, UK.
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Whatmore
Institute of Biomedical & Clinical Science, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
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Richardson
Institute of Biomedical & Clinical Science, University of Exeter Medical School, RILD Building, Barrack Road, Exeter EX2 5DW, UK. Electronic address: h.j.welters@exeter.ac.uk.
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Welters
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C495268:Ctnnb1 protein, rat; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C555581:WNT4 protein, human; D060509:Wnt3A Protein; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D051176:beta Catenin; D005947:Glucose
Cell growth control; Insulin secretion; Islet cells; Wnt signalling; Wnt4