{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:47:31Z","timestamp":1792453651638,"version":"4.5.0"},"reference-count":25,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":3987,"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":[[2010,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Inducing human \u03b2-cell growth while enhancing function is a major goal in the treatment of diabetes. Parathyroid hormone\u2013related protein (PTHrP) enhances rodent \u03b2-cell growth and function through the parathyroid hormone-1 receptor (PTH1R). Based on this, we hypothesized that PTH1R is expressed in human \u03b2-cells and that PTHrP has the potential to enhance human \u03b2-cell proliferation and\/or function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>PTH1R expression, \u03b2-cell proliferation, glucose-stimulated insulin secretion (GSIS), and expression of differentiation and cell-cycle genes were analyzed in human islets transduced with adenoviral PTHrP constructs or treated with PTHrP peptides. The effect of overexpression of late G1\/S cell cycle molecules was also assessed on human \u03b2-cell proliferation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>We found that human \u03b2-cells express PTH1R. More importantly, overexpression of PTHrP causes a significant approximately threefold increase in human \u03b2-cell proliferation. Furthermore, the amino terminus PTHrP(1-36) peptide is sufficient to increase replication as well as expression of the late G1\/S cell-cycle proteins cyclin E and cyclin-dependent kinase 2 (cdk2) in human islets. Notably, PTHrP(1-36) also enhances GSIS. Finally, overexpression of cyclin E alone, but not cdk2, augments human \u03b2-cell proliferation, and when both molecules are expressed simultaneously there is a further marked synergistic increase in replication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>PTHrP(1-36) peptide enhances human \u03b2-cell proliferation as well as function, with associated upregulation of two specific cell-cycle activators that together can induce human \u03b2-cell proliferation several fold. The future therapeutic potential of PTHrP(1-36) for the treatment of diabetes is especially relevant given the complementary therapeutic efficacy of PTHrP(1-36) in postmenopausal osteoporosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db09-1796","type":"journal-article","created":{"date-parts":[[2010,9,29]],"date-time":"2010-09-29T02:36:25Z","timestamp":1285727785000},"page":"3131-3138","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":68,"title":["Parathyroid Hormone\u2013Related Protein Enhances Human \u03b2-Cell Proliferation and Function With Associated Induction of Cyclin-Dependent Kinase 2 and Cyclin E Expression"],"prefix":"10.2337","volume":"59","author":[{"given":"Nagesha","family":"Guthalu Kondegowda","sequence":"first","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Joshi-Gokhale","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Harb","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katoura","family":"Williams","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen K.","family":"Takane","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pili","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald K.","family":"Scott","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Stewart","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Garcia-Oca\u00f1a","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupangi C.","family":"Vasavada","sequence":"additional","affiliation":[{"name":"From the Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2010,9,28]]},"reference":[{"key":"2022031217544862800_B1","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.2337\/db07-1369","article-title":"\u03b2-Cell replication is the primary mechanism subserving the postnatal expansion of \u03b2-cell mass in 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