{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:02:38Z","timestamp":1791356558207,"version":"4.3.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,8]]},"abstract":"<jats:p>\n                    Regulation of pancreatic \u03b2 cell mass and function is a major determinant for the development of diabetes. Growth factors and nutrients are important regulators of \u03b2 cell mass and function. The signaling pathways by which these growth signals modulate these processes have not been completely elucidated. Tsc2 is an attractive candidate to modulate these processes, because it is a converging point for growth factor and nutrient signals. In these experiments, we generated mice with conditional deletion of\n                    <jats:italic>Tsc2<\/jats:italic>\n                    in \u03b2 cells (\u03b2\n                    <jats:italic>Tsc2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ). These mice exhibited decreased glucose levels and hyperinsulinemia in the fasting and fed state. Improved glucose tolerance in these mice was observed as early as 4 weeks of age and was still present in 52-week-old mice. Deletion of\n                    <jats:italic>Tsc2<\/jats:italic>\n                    in \u03b2 cells induced expansion of \u03b2 cell mass by increased proliferation and cell size. Rapamycin treatment reversed the metabolic changes in \u03b2\n                    <jats:italic>Tsc2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice by induction of insulin resistance and reduction of \u03b2 cell mass. The reduction of \u03b2 cell mass in \u03b2\n                    <jats:italic>Tsc2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice by inhibition of the mTOR\/Raptor (TORC1) complex with rapamycin treatment suggests that TORC1 mediates proliferative and growth signals induced by deletion of\n                    <jats:italic>Tsc2<\/jats:italic>\n                    in \u03b2 cells. These studies uncover a critical role for the Tsc2\/mTOR pathway in regulation of \u03b2 cell mass and carbohydrate metabolism\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803047105","type":"journal-article","created":{"date-parts":[[2008,6,27]],"date-time":"2008-06-27T21:23:48Z","timestamp":1214601828000},"page":"9250-9255","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":181,"title":["Disruption of Tsc2 in pancreatic \u03b2 cells induces \u03b2 cell mass expansion and improved glucose tolerance in a TORC1-dependent manner"],"prefix":"10.1073","volume":"105","author":[{"given":"Latif","family":"Rachdi","sequence":"first","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Balcazar","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Osorio-Duque","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Elghazi","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Weiss","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Gould","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen J.","family":"Chang-Chen","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Gambello","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, University of Texas Health Science Center, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Bernal-Mizrachi","sequence":"additional","affiliation":[{"name":"*Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00514.2001"},{"key":"e_1_3_3_2_2","first-page":"4047","article-title":"Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes","volume":"86","author":"Kahn SE","year":"2001","unstructured":"SE Kahn, Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. 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