{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:06:18Z","timestamp":1775693178293,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inadequate <jats:italic>\u03b2<\/jats:italic>\u2010cell mass is essential for the pathogenesis of type 2 diabetes (T2D). Previous report showed that an immunomodulator FTY720, a sphingosine 1\u2010phosphate (S1P) receptor modulator, sustainably normalized hyperglycemia by stimulating <jats:italic>\u03b2<\/jats:italic>\u2010cell in vivo regeneration in <jats:italic>db\/db<\/jats:italic> mice. We further examined the effects of FTY720 on glucose homeostasis and diabetic complications in a translational nonhuman primate (NHP) model of spontaneously developed diabetes. The male diabetic cynomolgus macaques of 18\u201319\u2009year old were randomly divided into Vehicle (Purified water, <jats:italic>n<\/jats:italic>\u2009=\u20095) and FTY720 (5\u2009mg\/kg, <jats:italic>n<\/jats:italic>\u2009=\u20097) groups with oral gavage once daily for 10\u2009weeks followed by 10\u2009weeks drug free period. Compared with the Vehicle group, FTY720 effectively lowered HbA1c, blood concentrations of fasting glucose (FBG) and insulin, hence, decreased homeostatic model assessment of insulin resistance (HOMA\u2010IR); ameliorated glucose intolerance and restored glucose\u2010stimulated insulin release, indicating rejuvenation of <jats:italic>\u03b2<\/jats:italic>\u2010cell function in diabetic NHPs. Importantly, after withdrawal of FTY720, FBG, and HbA1c remained at low level in the drug free period. Echocardiography revealed that FTY720 significantly reduced proteinuria and improved cardiac left ventricular systolic function measured by increased ejection fraction and fractional shortening in the diabetic NHPs. Finally, flow cytometry analysis (FACS) detected that FTY720 significantly reduced CD4\u2009+\u2009and CD8\u2009+\u2009T lymphocytes as well as increased DC cells in the circulation. Immunomodulator FTY720 improves glucose homeostasis via rejuvenation of <jats:italic>\u03b2<\/jats:italic>\u2010cell function, which can be mediated by suppression of cytotoxic CD8\u2009+\u2009T lymphocytes to <jats:italic>\u03b2<\/jats:italic>\u2010cells, thus, may be a novel immunotherapy to reverse T2D progression and ameliorate the diabetic complications.<\/jats:p>","DOI":"10.1111\/fcp.12760","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T01:48:46Z","timestamp":1642816126000},"page":"699-711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunomodulator FTY720 improves glucose homeostasis and diabetic complications by rejuvenation of <i>\u03b2<\/i>\u2010cell function in nonhuman primate model of diabetes"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3466-429X","authenticated-orcid":false,"given":"Yixin (Jim)","family":"Wang","sequence":"first","affiliation":[{"name":"Crown Bioscience Inc.  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