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Published on: December 7, 2017
The fractalkine/CX3CR1 system regulates β cell function and insulin secretion
Yun Sok Lee1, Hidetaka Morinaga, Jane J Kim
1Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA.
Cell
|April 16, 2013
Summary
The fractalkine (FKN)/CX3CR1 system regulates pancreatic islet beta cell function and insulin secretion. Impaired FKN/CX3CR1 signaling contributes to beta cell dysfunction in type 2 diabetes.
Area of Science:
- Endocrinology
- Immunology
- Metabolic Diseases
Background:
- Pancreatic islet beta cell dysfunction is central to type 2 diabetes.
- The role of the fractalkine (FKN)/CX3CR1 signaling pathway in beta cell function is not well understood.
Purpose of the Study:
- To investigate the role of the FKN/CX3CR1 system in regulating pancreatic islet beta cell function and insulin secretion.
- To explore the potential of FKN/CX3CR1 signaling as a therapeutic target for type 2 diabetes.
Main Methods:
- Utilized CX3CR1 knockout (KO) mice and wild-type (WT) littermates.
- Assessed glucose and GLP1-stimulated insulin secretion in vivo and in vitro.
- Administered FKN in vivo and in vitro to evaluate its effects on glucose tolerance and insulin secretion.
- Analyzed gene expression in isolated islets from KO and WT mice, and FKN-treated WT islets.
Main Results:
- CX3CR1 KO mice showed impaired glucose and GLP1-stimulated insulin secretion.
- In vivo FKN administration improved glucose tolerance and increased insulin secretion.
- In vitro FKN treatment of islets enhanced intracellular Ca(2+) and potentiated insulin secretion in mouse and human islets.
- KO islets had reduced expression of key beta cell function genes, while FKN treatment increased their expression in WT islets.
- Islet FKN expression decreased with aging and high-fat diet/obesity.
Conclusions:
- The FKN/CX3CR1 system is a critical regulator of pancreatic islet beta cell function and insulin secretion.
- Reduced FKN/CX3CR1 signaling, observed in aging and obesity, may contribute to beta cell dysfunction in type 2 diabetes.
- Modulating the FKN/CX3CR1 pathway holds potential for treating type 2 diabetes.
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