title: Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMS) in diabetic mice after prolonged high-fat diet.
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.
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.|Institute of Biology, College of Nursing, University of Pernambuco (UPE), Recife, PE, Brazil.
authors.forename: Viviane Tannuri F L
authors.initials: VT
authors.lastname: Falcão
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Maschio
authors.affiliation: Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.
authors.forename: Camila Calvo
authors.initials: CC
authors.lastname: de Fontes
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.|Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Junia C
authors.initials: JC
authors.lastname: Santos-Silva
authors.affiliation: Department of Biology, Federal University of Pernambuco (UFRPE), Recife, PE, Brazil.
authors.forename: Anna Carolina Soares
authors.initials: AC
authors.lastname: Almeida
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Emerielle C
authors.initials: EC
authors.lastname: Vanzela
authors.affiliation: Institute of Biology, College of Nursing, University of Pernambuco (UPE), Recife, PE, Brazil.
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: Cartaxo
authors.affiliation: Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.
authors.forename: Carolina P F
authors.initials: CP
authors.lastname: Carvalho
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil. collares@unicamp.br.
authors.forename: Carla Beatriz
authors.identifier: http://orcid.org/0000-0002-3269-9261
authors.initials: CB
authors.lastname: Collares-Buzato
mesh_terms: D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D051177:Catenins / Q000032:analysis / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062826:Zonula Occludens-1 Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D007328:Insulin; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein
keywords: Cell adhesion molecules; Cell–cell interactions; High-fat diet; Insulin secretion; Pancreatic beta cells; Type 2 diabetes mellitus