{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:54Z","timestamp":1784557254273,"version":"3.55.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>\n                    Mutations in the pancreatic duodenal homeobox (\n                    <jats:italic>PDX1<\/jats:italic>\n                    ) gene are associated with diabetes in humans.\n                    <jats:italic>Pdx1<\/jats:italic>\n                    -haploinsufficient mice also develop diabetes, but the molecular mechanism is unknown. To this end, we knocked down\n                    <jats:italic>Pdx1<\/jats:italic>\n                    gene expression in mouse MIN6 insulinoma cells. Pdx1 suppression not only increased apoptotic cell death but also decreased cell proliferation, which was associated with a decrease in activity of mechanistic target of rapamycin complex 1 (mTORC1). We found that in\n                    <jats:italic>Pdx1<\/jats:italic>\n                    -deficient mice, tuberous sclerosis 1 (\n                    <jats:italic>Tsc1<\/jats:italic>\n                    ) ablation in pancreatic \u03b2-cells restores \u03b2-cell mass, increases \u03b2-cell proliferation and size, decreases the number of TUNEL-positive cells and restores glucose tolerance after glucose challenge. In addition,\n                    <jats:italic>Tsc1<\/jats:italic>\n                    ablation in pancreatic \u03b2-cells increases phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation and 40S ribosomal protein S6, two downstream targets of mTORC1 indicating that Tsc1 mediates mTORC1 downregulation induced by Pdx1 suppression. These results suggest that the Tsc1-mTORC1 pathway plays an important role in mediating the decrease in \u03b2-cell proliferation and growth and the reduction in \u03b2-cell mass that occurs in Pdx1-deficient diabetes. Thus, mTORC1 may be target for therapeutic interventions in diabetes associated with reductions in \u03b2-cell mass.\n                  <\/jats:p>","DOI":"10.1530\/joe-18-0015","type":"journal-article","created":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T12:20:57Z","timestamp":1528287657000},"page":"151-163","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":4,"title":["Critical role for the Tsc1-mTORC1 pathway in \u03b2-cell mass in Pdx1-deficient mice"],"prefix":"10.1530","volume":"238","author":[{"given":"Juan","family":"Sun","sequence":"first","affiliation":[{"name":"1Department of Medicine, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Mao","sequence":"additional","affiliation":[{"name":"1Department of Medicine, The University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Yang","sequence":"additional","affiliation":[{"name":"2Department of Gynecology, Key Research Laboratory of Gynecology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decheng","family":"Ren","sequence":"additional","affiliation":[{"name":"1Department of Medicine, The University of Chicago, Chicago, Illinois, USA"},{"name":"2Department of Gynecology, Key Research Laboratory of Gynecology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref331","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1371\/journal.pbio.0060037","article-title":"Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin 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