期刊
CELL
卷 153, 期 2, 页码 413-425出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.03.001
关键词
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资金
- National Institutes of Health (NIH) [DK-033651, DK-074868, T32-DK-007494, DK-063491]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH as part of the specialized Cooperative Centers Program in Reproduction and Infertility Research [U54-HD-012303-25]
- American Diabetes Association
Here, we demonstrate that the fractalkine (FKN)/CX3CR1 system represents a regulatory mechanism for pancreatic islet beta cell function and insulin secretion. CX3CR1 knockout (KO) mice exhibited a marked defect in glucose and GLP1-stimulated insulin secretion, and this defect was also observed in vitro in isolated islets from CX3CR1 KO mice. In vivo administration of FKN improved glucose tolerance with an increase in insulin secretion. In vitro treatment of islets with FKN increased intracellular Ca2+ and potentiated insulin secretion in both mouse and human islets. The KO islets exhibited reduced expression of a set of genes necessary for the fully functional, differentiated b cell state, whereas treatment of wild-type (WT) islets with FKN led to increased expression of these genes. Lastly, expression of FKN in islets was decreased by aging and high-fat diet/obesity, suggesting that decreased FKN/CX3CR1 signaling could be a mechanism underlying b cell dysfunction in type 2 diabetes.
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