{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:55:29Z","timestamp":1790880929263,"version":"4.1.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"4","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Obestatin is a newly discovered peptide encoded by the ghrelin gene whose biological functions are poorly understood. We investigated obestatin effect on survival of \u03b2-cells and human pancreatic islets and the underlying signaling pathways.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014\u03b2-Cells and human islets were used to assess obestatin effect on cell proliferation, survival, apoptosis, intracellular signaling, and gene expression.<\/jats:p>\n               <jats:p>RESULTS\u2014Obestatin showed specific binding on HIT-T15 and INS-1E \u03b2-cells, bound to glucagon-like peptide-1 receptor (GLP-1R), and recognized ghrelin binding sites. Obestatin exerted proliferative, survival, and antiapoptotic effects under serum-deprived conditions and interferon-\u03b3\/tumor necrosis factor-\u03b1\/interleukin-1\u03b2 treatment, particularly at pharmacological concentrations. Ghrelin receptor antagonist [D-Lys3]-growth hormone releasing peptide-6 and anti-ghrelin antibody prevented obestatin-induced survival in \u03b2-cells and human islets. \u03b2-Cells and islet cells released obestatin, and addition of anti-obestatin antibody reduced their viability. Obestatin increased \u03b2-cell cAMP and activated extracellular signal\u2013related kinase 1\/2 (ERK1\/2) and phosphatidylinositol 3-kinase (PI 3-kinase)\/Akt; its antiapoptotic effect was blocked by inhibition of adenylyl cyclase\/cAMP\/protein kinase A (PKA), PI 3-kinase\/Akt, and ERK1\/2 signaling. Moreover, obestatin upregulated GLP-1R mRNA and insulin receptor substrate-2 (IRS-2) expression and phosphorylation. The GLP-1R antagonist exendin-(9-39) reduced obestatin effect on \u03b2-cell survival. In human islets, obestatin, whose immunoreactivity colocalized with that of ghrelin, promoted cell survival and blocked cytokine-induced apoptosis through cAMP increase and involvement of adenylyl cyclase\/cAMP\/PKA signaling. Moreover, obestatin 1) induced PI 3-kinase\/Akt, ERK1\/2, and also cAMP response element\u2013binding protein phosphorylation; 2) stimulated insulin secretion and gene expression; and 3) upregulated GLP-1R, IRS-2, pancreatic and duodenal homeobox-1, and glucokinase mRNA.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014These results indicate that obestatin promotes \u03b2-cell and human islet cell survival and stimulates the expression of main regulatory \u03b2-cell genes, identifying a new role for this peptide within the endocrine pancreas.<\/jats:p>","DOI":"10.2337\/db07-1104","type":"journal-article","created":{"date-parts":[[2007,12,28]],"date-time":"2007-12-28T01:24:20Z","timestamp":1198805060000},"page":"967-979","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":153,"title":["Obestatin Promotes Survival of Pancreatic \u03b2-Cells and Human Islets and Induces Expression of Genes Involved in the Regulation of \u03b2-Cell Mass and Function"],"prefix":"10.2337","volume":"57","author":[{"given":"Riccarda","family":"Granata","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Settanni","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Gallo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Trovato","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Biancone","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Cantaluppi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Nano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Transplant Unit, Scientific Institute San Raffaele, Vita-Salute University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Salerno, Fisciano (Salerno), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Arnoletti","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Ghe\u0300","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Volante","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences and San Luigi Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Papotti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences and San Luigi Hospital, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampiero","family":"Muccioli","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezio","family":"Ghigo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209211370700_R1","doi-asserted-by":"crossref","unstructured":"Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ: Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. 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