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Fractalkine Treatment Alleviates Symptoms of Type II Diabetes

By BiotechDaily International staff writers
Posted on 23 Apr 2013
Treatment of mouse diabetes models and in vitro cultures of human pancreatic cells with the protein fractalkine alleviated symptoms of type II diabetes by increasing insulin secretion and improving glucose tolerance.

Fractalkine (also known as chemokine (C-X3-C motif) ligand 1) is produced as a long 373-amino acid protein with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the surface of certain cells. Furthermore, a soluble (90-kDa) version of this chemokine has also been observed. Soluble fractalkine potently attracts T-cells and monocytes, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed. Fractalkine elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.

Investigators at the University of California, San Diego (USA) studied the role of fractalkine in type II diabetes using a mouse model that had been genetically engineered to lack the gene for production of the fractalkine receptor CX3CR1. They reported in the April 11, 2013, issue of the journal Cell that these knockout mice exhibited a marked defect in glucose and GLP1 (glucagon-like peptide-1)-stimulated insulin secretion, and this defect was also observed in vitro in isolated pancreatic islets from CX3CR1 knockout mice. Pancreatic islet cells from the knockout mice exhibited reduced expression of a set of genes necessary for the fully functional, differentiated beta cell state, whereas treatment of wild-type (WT) islets with fractalkine led to increased expression of these genes.

Expression of fractalkine in islets was decreased by aging, high-fat diet, and obesity. In vitro treatment of islets with fractalkine increased intracellular calcium ion levels and potentiated insulin secretion in both mouse and human islets.

"Our discovery of fractalkine's role in beta cells is novel and has never been talked about in prior literature," said senior author Dr. Jerrold M. Olefsky, professor of medicine at the University of California, San Diego. "Whether or not decreased fractalkine or impaired fractalkine signaling are causes of decreased beta cell function in diabetes is unknown. What we do know, without doubt, is that administration of fractalkine improves or restores insulin secretion in all of the mouse models we have examined, as well as in human islet cells. If successfully developed, this could be an important new complement to the therapeutic arsenal we use in type II diabetes. It is not likely to cure diabetes, but it would certainly do a good job at providing glycemic control."

Related Links:
University of California, San Diego



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