{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:38:09Z","timestamp":1792690689571,"version":"4.5.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3811,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,4,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 has recently been linked to type 2 diabetes by genome-wide association studies. While CDK5 and its regulatory protein p35 are both expressed and display enzymatic activity in pancreatic \u03b2-cells, their precise role in the \u03b2-cell remains unknown. Because type 2 diabetes is characterized by a deficit in \u03b2-cell mass and increased \u03b2-cell apoptosis, we investigated the role of CDK5 in \u03b2-cell survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We used INS 832\/13 cells, rat islets isolated from wild-type or human islet amyloid polypeptide (h-IAPP) transgenic rats, and pancreatic tissue from rats and humans with and without type 2 diabetes and investigated the effect of CDK5\/p35 inhibition (by small interfering RNA or by chemical inhibition) as well as CDK5\/p35 overexpression on \u03b2-cell vulnerability to apoptosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>CDK5 inhibition led to increased \u03b2-cell apoptosis. To identify the mechanisms involved, we examined the phosphorylation state of focal adhesion kinase (Fak)Ser732, a known target of CDK5. Following CDK5 inhibition, the phosphorylation of FakSer732 decreased with resulting attenuation of phosphatidylinositol 3-kinase (PI3K)\/Akt survival pathway. Conversely, CDK5 overexpression increased FakSer732 phosphorylation and protected \u03b2-cells against apoptosis induced by the inhibition of the \u03b2-1 integrin signaling pathway. Also, FakSer732 phosphorylation was less abundant in \u03b2-cells in both h-IAPP transgenic rats and humans with type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study shows that by regulating Fak phosphorylation and subsequently PI3K\/Akt survival pathway, CDK5 plays a previously unrecognized role in promoting \u03b2-cell survival.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db10-1048","type":"journal-article","created":{"date-parts":[[2011,3,5]],"date-time":"2011-03-05T03:34:24Z","timestamp":1299296064000},"page":"1186-1197","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":44,"title":["Cyclin-Dependent Kinase 5 Promotes Pancreatic \u03b2-Cell Survival via Fak-Akt Signaling Pathways"],"prefix":"10.2337","volume":"60","author":[{"given":"Marie","family":"Daval","sequence":"first","affiliation":[{"name":"Larry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Gurlo","sequence":"additional","affiliation":[{"name":"Larry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safia","family":"Costes","sequence":"additional","affiliation":[{"name":"Larry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-jiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Larry Hillblom Islet Research Center, David 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