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

Author(s)

Falcao, Viviane Tannuri F. L. ^{[1, 2]} ; Maschio, Daniela A. ^[1] ; de Fontes, Camila Calvo ^[3] ; Oliveira, Ricardo B. ^[1] ; Santos-Silva, Junia C. ^{[4, 1]} ; Soares Almeida, Anna Carolina ^[5] ; Vanzela, Emerielle C. ^[4] ; Cartaxo, Maria Tereza ^[2] ; Carvalho, Carolina P. F. ^[3] ; Collares-Buzato, Carla Beatriz ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil

^[2] Univ Pernambuco UPE, Coll Nursing, Inst Biol, Recife, PE - Brazil

^[3] Univ Fed Sao Paulo, Dept Biosci, Santos, SP - Brazil

^[4] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083970 Campinas, SP - Brazil

^[5] Fed Univ Pernambuco UFRPE, Dept Biol, Recife, PE - Brazil

• Document type: Journal article
• Source: Histochemistry and Cell Biology; v. 146, n. 1, p. 13-31, JUL 2016.
• Web of Science Citations: 11

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. (AU)

• FAPESP's process: 10/50789-1 - Role of cell-cell contacts mediated by intercellular junctions and their constitutive proteins in the functional maturation and dysfunction of pancreatic beta cells
• Grantee: Carla Beatriz Collares Buzato
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/54129-9 - Central Laboratory of High-Performance Technologies in the life sciences
• Grantee: Paulo Arruda
• Support Opportunities: Multi-user Equipment Program