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Histochem Cell Biol. 2016 Jul;146(1):13-31. doi: 10.1007/s00418-016-1428-5. Epub 2016 Mar 28.

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

Author information

1
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.
2
Institute of Biology, College of Nursing, University of Pernambuco (UPE), Recife, PE, Brazil.
3
Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.
4
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
5
Department of Biology, Federal University of Pernambuco (UFRPE), Recife, PE, Brazil.
6
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil. collares@unicamp.br.

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, α- and β-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 α-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 α-catenin and F-actin is significantly altered in islet cells of obese and diabetic mice.

KEYWORDS:

Cell adhesion molecules; Cell–cell interactions; High-fat diet; Insulin secretion; Pancreatic beta cells; Type 2 diabetes mellitus

PMID:
27020567
DOI:
10.1007/s00418-016-1428-5
[Indexed for MEDLINE]

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