Related Experiment Video
Updated: Jul 16, 2026
Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation
Published on: August 7, 2015
Changes in expression of P2X7 receptors in NOD mouse pancreas during the development of diabetes
Robson Coutinho-Silva1, Tim Robson, Philip E Beales
1Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London, UK.
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 (alpha-cells), insulin (beta-cells) and somatostatin (delta-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 alpha-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 alpha- and beta-cell populations. P2X7 receptor signalling might be involved in alpha-cell clearance from late diabetic islets.
Insights
P2X7 receptors decrease in pancreatic islets during diabetes development in NOD mice, leading to alpha- and beta-cell loss. This suggests P2X7 receptor signaling may drive alpha-cell destruction in late-stage diabetes.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- The non-obese diabetic (NOD) mouse model mimics human autoimmune insulin-dependent diabetes mellitus.
- Pancreatic islet cells (alpha, beta, delta) express various receptors, including P2X7.
- Understanding P2X7 receptor involvement in islet cell destruction is crucial for diabetes research.
Purpose of the Study:
- To investigate P2X7 receptor expression in pancreatic islets of NOD mice.
- To determine the role of P2X7 receptors in islet cell destruction during early and late diabetes.
- To correlate P2X7 receptor changes with alpha- and beta-cell population dynamics.
Main Methods:
- Co-localization studies of P2X7 receptors with glucagon, insulin, and somatostatin in pancreatic islets.
- Flow cytometry analysis of P2X7 receptor expression in splenic macrophages from control and diabetic NOD mice.
- Comparative analysis of P2X7 receptor expression at different stages of diabetes (12 and 34 weeks).
Main Results:
- P2X7 receptors were initially found on peripheral glucagon-containing cells in non-diabetic NOD mice.
- In early diabetes, P2X7 receptor-positive cells migrated centrally within islets.
- Late-stage diabetes showed a complete loss of P2X7 receptor- and glucagon-stained alpha-cells, with unaffected splenic macrophage P2X7 expression.
Conclusions:
- A down-regulation of P2X7 receptors on islet cells occurs during diabetes progression in NOD mice.
- The study observed a significant loss of alpha- and beta-cell populations correlating with P2X7 receptor changes.
- P2X7 receptor signaling is implicated in the clearance of alpha-cells from islets in late-stage diabetes.
Related Concept Videos
01:21Chronic Pancreatitis II: Pathophysiology
01:24Type II Diabetes II: Pathophysiology