Human placental lactogen (hPL-A) activates signaling pathways linked to cell survival and improves insulin secretion in human pancreatic islets

Autor: Massimo Federici, Renato Lauro, Barbara Bartolini, Luca Bova, Marco F. Lombardo, Davide Lauro, Fabiana De Angelis, Federico Bertuzzi, Barbara Capuani, Giulia Donadel, Rita Nano
Rok vydání: 2011
Předmět:
endocrine system
medicine.medical_specialty
Settore MED/09 - Medicina Interna
Cell Survival
MAP Kinase Signaling System
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Settore MED/50 - Scienze Tecniche Mediche Applicate
Apoptosis
Biology
p38 Mitogen-Activated Protein Kinases
Settore MED/13 - Endocrinologia
Mice
Endocrinology
Human placental lactogen
Cell Line
Tumor
Insulin-Secreting Cells
Internal medicine
Insulin Secretion
medicine
Animals
Humans
Insulin
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
Extracellular Signal-Regulated MAP Kinases
Insulinoma
Protein kinase B
PI3K/AKT/mTOR pathway
Settore MED/04 - Patologia Generale
Human Growth Hormone
Pancreatic islets
Placental Lactogen
medicine.disease
Prolactin
Rats
Pancreatic Neoplasms
medicine.anatomical_structure
Beta cell
Signal transduction
Proto-Oncogene Proteins c-akt
Research Paper
Zdroj: Islets. 3:250-258
ISSN: 1938-2022
1938-2014
Popis: 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.
Databáze: OpenAIRE
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