Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet

Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet

Author Falcao, Viviane Tannuri F. L. Google Scholar
Maschio, Daniela A. Google Scholar
de Fontes, Camila Calvo Autor UNIFESP Google Scholar
Oliveira, Ricardo B. Google Scholar
Santos-Silva, Junia C. Google Scholar
Soares Almeida, Anna Carolina Google Scholar
Vanzela, Emerielle C. Google Scholar
Cartaxo, Maria Tereza Google Scholar
Carvalho, Carolina P. F. Autor UNIFESP Google Scholar
Collares-Buzato, Carla Beatriz Google Scholar
Abstract Intercellular junctions play a role in regulating islet cytoarchitecture, insulin biosynthesis and secretion. In this study, we investigated the animal metabolic state as well as islet histology and cellular distribution/expression of CAMs and F-actin in the endocrine pancreas of C57BL/6/JUnib mice fed a high-fat diet (HFd) for a prolonged time period (8 months). Mice fed a HFd became obese and type 2 diabetic, displaying significant peripheral insulin resistance, hyperglycemia and moderate hyperinsulinemia. Isolated islets of HFd-fed mice displayed a significant impairment of glucose-induced insulin secretion associated with a diminished frequency of intracellular calcium oscillations compared with control islets. No marked change in islet morphology and cytoarchitecture was observed

however, HFd-fed mice showed higher beta cell relative area in comparison with controls. As shown by immunohistochemistry, ZO-1, E-, N-cadherins, alpha- and beta-catenins were expressed at the intercellular contact site of endocrine cells, while VE-cadherin, as well as ZO-1, was found at islet vascular compartment. Redistribution of N-, E-cadherins and alpha-catenin (from the contact region to the cytoplasm in endocrine cells) associated with increased submembranous F-actin cell level as well as increased VE-cadherin islet immunolabeling was observed in diabetic mice. Increased gene expression of VE-cadherin and ZO-1, but no change for the other proteins, was observed in islets of diabetic mice. Only in the case of VE-cadherin, a significant increase in islet content of this CAM was detected by immunoblotting in diabetic mice. In conclusion, CAMs are expressed by endocrine and endothelial cells of pancreatic islets. The distribution/expression of N-, E- and VE-cadherins as well as alpha-catenin and F-actin is significantly altered in islet cells of obese and diabetic mice.
Keywords Cell adhesion molecules
Cell-cell interactions
Pancreatic beta cells
Type 2 diabetes mellitus
High-fat diet
Insulin secretion
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor FAPESP
PhD CAPES-DINTER fellowship (Brazil)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil
Grant number FAPESP: 2010/50789-1
CNPq: 307163/2012-1
CNPq: 304991/2015-5
Date 2016
Published in Histochemistry And Cell Biology. New York, v. 146, n. 1, p. 13-31, 2016.
ISSN 0948-6143 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 13-31
Access rights Closed access
Type Article
Web of Science ID WOS:000378785900002

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