| Autor: |
Ballesteros-Pla, Cristina, Sevillano, Julio, Sánchez-Alonso, María Gracia, Limones, María, Pita, Jimena, Zapatería, Begoña, Sanz-Cuadrado, Marta Inmaculada, Pizarro-Delgado, Javier, Izquierdo-Lahuerta, Adriana, Medina-Gómez, Gema, Herradón, Gonzalo, Ramos-Álvarez, María del Pilar |
| Zdroj: |
International Journal of Molecular Sciences; Oct2024, Vol. 25 Issue 20, p10960, 19p |
| Abstrakt: |
Pleiotrophin (PTN) is crucial for embryonic development and pancreas organogenesis as it regulates metainflammation, metabolic homeostasis, thermogenesis, and glucose tolerance. Pleiotrophin deletion is associated with a lipodystrophic phenotype in which adipose tissue plasticity is altered in late life. This study explored the impact of pleiotrophin deletion on pancreatic morphology and function in later life. We analyzed glucose tolerance and circulating parameters on female wild-type (Ptn+/+) and knock-out (Ptn−/−) mice. At 9 and 15 months, we conducted morphometric analyses of pancreatic islets and evaluated the levels of insulin, glucagon, somatostatin, glucose transporter 2 (GLUT2), vesicle-associated membrane protein 2 (VAMP2), and synaptosome-associated protein 25 (SNAP25) via immunofluorescence. The effect of PTN on glucose-stimulated insulin secretion (GSIS) was evaluated in INS1E cells and isolated islets. Ptn−/− mice showed hyperinsulinemia, impaired glucose tolerance, and increased homeostatic model assessment for insulin resistance (HOMA-IR) with age. While Ptn+/+ islets enlarge with age, in Ptn−/− mice, the median size decreased, and insulin content increased. Vesicle transport and exocytosis proteins were significantly increased in 9-month-old Ptn−/− islets. Islets from Ptn−/− mice showed impaired GSIS and decreased cell membrane localization of GLUT2 whereas, PTN increased GSIS in INS1E cells. Ptn deletion accelerated age-related changes in the endocrine pancreas, affecting islet number and size, and altering VAMP2 and SNAP25 levels and GLUT2 localization leading to impaired GSIS and insulin accumulation in islets. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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