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

Falcão, Viviane; Maschio, Daniela; Fontes, Camila; Oliveira, Ricardo; Santos-Silva, Junia; Almeida, Anna; Vanzela, Emerielle; Cartaxo, Maria; Carvalho, Carolina; Collares-Buzato, Carla

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.

ANIMAL models of diabetes; PHYSIOLOGICAL effects of insulin; CELL adhesion molecules; HIGH-fat diet; INSULIN resistance; HYPERINSULINISM; IMMUNOHISTOCHEMISTRY; CADHERINS

Histochemistry & Cell Biology, 2016, Vol 146, Issue 1, p13

0948-6143

Academic Journal

10.1007/s00418-016-1428-5