{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:22:20Z","timestamp":1792570940503,"version":"4.5.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100011199","name":"European Research Council","doi-asserted-by":"publisher","award":["336204"],"award-info":[{"award-number":["336204"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,3,1]]},"abstract":"<jats:p>Polymorphism in TCF7L2, a component of the canonical Wnt signaling pathway, has a strong association with \u03b2-cell dysfunction and type 2 diabetes through a mechanism that has yet to be defined. \u03b2-Cells rely on cells in their microenvironment, including pericytes, for their proper function. Here, we show that Tcf7l2 activity in pancreatic pericytes is required for \u03b2-cell function. Transgenic mice in which Tcf7l2 was selectively inactivated in their pancreatic pericytes exhibited impaired glucose tolerance due to compromised \u03b2-cell function and glucose-stimulated insulin secretion. Inactivation of pericytic Tcf7l2 was associated with impaired expression of genes required for \u03b2-cell function and maturity in isolated islets. In addition, we identified Tcf7l2-dependent pericytic expression of secreted factors shown to promote \u03b2-cell function, including bone morphogenetic protein 4 (BMP4). Finally, we show that exogenous BMP4 is sufficient to rescue the impaired glucose-stimulated insulin secretion of transgenic mice, pointing to a potential mechanism through which pericytic Tcf7l2 activity affects \u03b2-cells. To conclude, we suggest that pancreatic pericytes produce secreted factors, including BMP4, in a Tcf7l2-dependent manner to support \u03b2-cell function. Our findings thus propose a potential cellular mechanism through which abnormal TCF7L2 activity predisposes individuals to diabetes and implicates abnormalities in the islet microenvironment in this disease.<\/jats:p>","DOI":"10.2337\/db17-0697","type":"journal-article","created":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T01:20:42Z","timestamp":1513387242000},"page":"437-447","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":53,"title":["Pancreatic Pericytes Support \u03b2-Cell Function in a Tcf7l2-Dependent Manner"],"prefix":"10.2337","volume":"67","author":[{"given":"Lina","family":"Sakhneny","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonor","family":"Rachi","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alona","family":"Epshtein","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Guez","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Wald-Altman","sequence":"additional","affiliation":[{"name":"Department of Cell Research and Immunology, The George S. 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