RT Journal Article
T1 The overexpression of human amylin in pancreatic β cells facilitate the appearance of amylin aggregates in the kidney contributing to diabetic nephropathy
A1 Iglesias-Fortes, S.
A1 González Blanco, Carlos
A1 García-Carrasco, A.
A1 Izquierdo-Lahuerta, A.
A1 García, G.
A1 García Aguilar, Ana
A1 Lockwood, A.
A1 Palomino Ruiz-Poveda, Olga María
A1 Medina-Gómez, G
A1 Benito León, María
A1 Guillén Viejo, Carlos
AB Diabetic nephropathy is one of the most frequent complications of diabetic patients and is the leading cause of end-stage renal disease worldwide. The complex physiopathology of this complication raises a challenge in the development of effective medical treatments. Therefore, a better understanding of this disease is necessary for producing more targeted therapies. In this work we propose human amylin as a possible mediator in the development of diabetic nephropathy. Islet amyloid polypeptide or amylin is a hormone co-secreted with insulin. The human isoform has the ability to fold and form amyloid aggregates in the pancreas of patients with type 2 diabetes mellitus, disrupting cellular homeostasis due to its ability to form pores in lipid bilayers. It has been described that hIAPP can be secreted and exported in extracellular vesicles outside the pancreas, being a plausible connecting mechanism between the β-cell and other peripheral tissues such as the kidney. Here, we demonstrate that tubular, podocytes and mesangial cells can incorporate hIAPP coming from β-cells. Then, this hIAPP can form aggregates inside these kidney cells, contributing to its failure. In order to study the consequences in vivo, we found amylin aggregates in the kidney of mice overexpressing hIAPP after feeding a high fat diet. In addition, we observed an increase in glomerulosclerosis index and inflammation. Specifically, there were significant changes in signalling pathways directly involved in the diabetic nephropathy such as an increased in mTORC1 signaling pathway, an alteration in mitochondrial dynamics and an increased in endoplasmic reticulum stress. All these results demonstrate the importance of hIAPP in the kidney and its possible contribution in the development of diabetic nephropathy.
PB Springer Nature
YR 2024
FD 2024-10-21
LK https://hdl.handle.net/20.500.14352/113937
UL https://hdl.handle.net/20.500.14352/113937
LA eng
NO Iglesias-Fortes, S., et al. «The Overexpression of Human Amylin in Pancreatic β Cells Facilitate the Appearance of Amylin Aggregates in the Kidney Contributing to Diabetic Nephropathy». Scientific Reports, vol. 14, n.o 1, octubre de 2024, p. 24729. DOI.org (Crossref), https://doi.org/10.1038/s41598-024-77063-9.
NO Ministerio de Ciencia e Innovación (España)
NO European Commission-ERC
NO Centro de investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
DS Docta Complutense
RD 10 abr 2025