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• W2891045565 abstract "The ability to manipulate the development of pancreatic insulin-producing β cells has implications for the treatment of type 1 diabetes. Previously, we found that laminin-1, a basement membrane trimeric glycoprotein, promotes β-cell differentiation. We have investigated the mechanism of this effect, using agents that block the receptors for laminin-1, α6 integrin, and α-dystroglycan (α-DG). Dissociated cells from 13.5-day postcoitum (dpc) fetal mouse pancreas were cultured for 4 days with laminin-1, with and without monoclonal antibodies and other agents known to block integrins or α-DG. Fetuses fixed in Bouin’s solution or fetal pancreas cells fixed in 4% paraformaldehyde were processed for routine histology and for immunohistology to detect hormone expression and bromodeoxyuridine (BrdU) uptake. Blocking the binding of laminin-1 to α6 integrin with a monoclonal antibody, GoH3, abolished cell proliferation (BrdU uptake) and doubled the number of β cells. Inhibition of molecules involved in α6 integrin signaling (phosphotidylinositol 3-kinase, F-actin, or mitogen-activated protein kinase) had a similar effect. Nevertheless, β cells appeared to develop normally in α6 integrin-deficient fetuses. Blocking the binding of laminin-1 to α-DG with a monoclonal antibody, IIH6, dramatically decreased the number of β cells. Heparin, also known to inhibit laminin-1 binding to α-DG, had a similar effect. In the presence of heparin, the increase in β cells in response to blocking α6 integrin with GoH3 was abolished. These findings reveal an interplay between α6 integrin and α-DG to regulate laminin-1-induced β-cell development. Laminin-1 had a dominant effect via α-DG to promote cell survival and β-cell differentiation, which was modestly inhibited by α6 signaling." @default.
• W2891045565 created "2018-09-27" @default.
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• W2891045565 date "2001-02-01" @default.
• W2891045565 modified "2023-10-13" @default.
• W2891045565 title "Regulation of Laminin 1-Induced Pancreatic β-Cell Differentiation by α6 Integrin and α-Dystroglycan" @default.
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• W2891045565 doi "https://doi.org/10.1007/bf03401944" @default.
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