title: Human placental lactogen (hPL-A) activates signaling pathways linked to cell survival and improves insulin secretion in human pancreatic islets.
abstract: The search for factors either promoting islets proliferation or survival during adult life is a major issue for both type 1 and 2 diabetes mellitus. Among factors with mitogenic activity on pancreatic β-cells, human placental lactogen (hPL) showed stronger activity when compared to the other lactogen hormones: growth hormone (GH) and prolactin (PRL). The aim of the present work is to elucidate the biological and molecular events of hPL isoform A (hPL-A) activity on human cultured islets. We used pure human pancreatic islets and insulinoma cell lines (βTC-1 and RIN, murine and rat respectively) stimulated with hPL-A recombinant protein and we compared hPL-A activity with that of hGH. We showed that hPL-A inhibits apoptosis, both in insulinoma and human islets, by the phosphorylation of AKT protein. Indeed, the antiapoptotic role of hPL-A was mediated by PI3K, p38 and it was independent by PKA, Erk1/2. Compared with hGH, hPL-A modulated at different intervals and/or intensity by the phosphorylation of JAKs/STATs and MAPKinases. Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation. Our data support the idea that hPL-A is involved in the regulation of beta cells activity. Importantly, we found that hPL-A can preserve and improve the ability of purified human pancreatic islets cultured to secrete insulin in vitro.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Marco F
authors.initials: MF
authors.lastname: Lombardo
authors.forename: Fabiana
authors.initials: F
authors.lastname: De Angelis
authors.forename: Luca
authors.initials: L
authors.lastname: Bova
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartolini
authors.forename: Federico
authors.initials: F
authors.lastname: Bertuzzi
authors.forename: Rita
authors.initials: R
authors.lastname: Nano
authors.forename: Barbara
authors.initials: B
authors.lastname: Capuani
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Giulia
authors.initials: G
authors.lastname: Donadel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007340:Insulinoma; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010190:Pancreatic Neoplasms; D010928:Placental Lactogen / Q000378:metabolism* / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007328:Insulin; D019382:Human Growth Hormone; D011388:Prolactin; D010928:Placental Lactogen; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases