Changes in expression of P2X₇ receptors in NOD mouse pancreas during the development of diabetes

Abstract

This study examined the expression of P2X₇ receptors in pancreatic islets of the non-obese diabetic (NOD) mouse model of human autoimmune insulin-dependent diabetes mellitus, to determine whether they are involved in islet cell destruction during early- and late-developing diabetes. Pancreatic cells containing glucagon (α-cells), insulin (β-cells) and somatostatin (δ-cells) were co-localized with P2X₇ receptors. We examined P2X₇ receptor expression in normal and diabetic spleens using flow cytometry. In non-diabetic NOD controls, P2X₇ receptors were expressed in glucagon-containing cells at the periphery of islets, being consistent with previous studies. In early NOD diabetes (12 weeks), there was migration of peripheral P2X₇ receptor positive, glucagon-containing cells into the center of islets. In late NOD diabetes (34 weeks), P2X₇ receptor- and glucagon-stained α-cells were gone from islets. Migration of macrophages and dendritic cells into islets took place, but they lacked P2X₇ immunoreactivity. There was no significant difference in the percentage of splenic macrophages stained for P2X₇ receptors from control and diabetic spleens. In conclusion, in the development of early to late diabetes, there is a down-regulation of P2X₇ receptors on islet cells and a loss of α- and β-cell populations. P2X₇ receptor signalling might be involved in α-cell clearance from late diabetic islets.

• Diabetes
• NOD
• P2X₇ receptors
• islet cells

Acknowledgements

Authors wish to thank Dr Doris Rosenthal for help with the Discussion and Dr Gillian E. Knight for editorial assistance with the manuscript. This work was supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico do Brasil (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and the Wellcome Trust. Dr Coutinho-Silva was a Wellcome Trust fellow, number 062754/Z00Z.