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

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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.

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Acknowledgments

The authors thank Célia Garcia for technical assistance, Luiza Martinez Perdigueiro for helping with morphometric analysis, and Profs. Antonio Carlos Boschero and Everardo Carneiro for the use of their laboratory facilities for RIE and intracellular calcium measurements. We thank the staff of the Hemocentro (Medical School) and Life Sciences Core Facility (LaCTAD) from University of Campinas (UNICAMP) for helping with confocal microscopy imaging. The confocal scanning laser microscopes used were acquired under the Grants # 2000/05137-4 and 2009/54129-9. This work was funded by grants from FAPESP (Grant # 2010/50789-1), CNPq, FAEPEX/UNICAMP and CAPES/PROEX (Brazil). VTFLF was recipient of a PhD CAPES-DINTER fellowship (Brazil). CBC-B are supported by a Research Fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil, Grants # 307163/2012-1; 304991/2015-5). This work has been presented at the 2014 Annual ASCB/IFCB Meeting and partially published in abstract form (Mol Biol Cel 25, 448 (Abstract # P591).

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    Authors and Affiliations

    1. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil

      Viviane Tannuri F. L. Falcão, Daniela A. Maschio, Ricardo B. Oliveira, Junia C. Santos-Silva & Carla Beatriz Collares-Buzato

    2. Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil

      Junia C. Santos-Silva & Emerielle C. Vanzela

    3. Institute of Biology, College of Nursing, University of Pernambuco (UPE), Recife, PE, Brazil

      Viviane Tannuri F. L. Falcão & Maria Tereza Cartaxo

    4. Department of Biology, Federal University of Pernambuco (UFRPE), Recife, PE, Brazil

      Anna Carolina Soares Almeida

    5. Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil

      Camila Calvo de Fontes & Carolina P. F. Carvalho

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    1. Viviane Tannuri F. L. Falcão
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    9. Carolina P. F. Carvalho
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    10. Carla Beatriz Collares-Buzato
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    Correspondence to Carla Beatriz Collares-Buzato.

    Additional information

    Viviane Tannuri F. L. Falcão and Daniela A. Maschio have contributed equally to this work.

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    Falcão, V.T.F.L., Maschio, D.A., de Fontes, C.C. et al. Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet. Histochem Cell Biol 146, 13–31 (2016). https://doi.org/10.1007/s00418-016-1428-5

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