Injection of recombinant fibroblast growth factor 1 (rFGF1) potently sensitizes insulin action, according to a new study by Ron Evans and his colleagues (Nature doi:10.1038/nature13540, 2014).
Deletion of the gene encoding FGF1 in mice is associated with insulin resistance, and agonist antibodies of FGF receptor modulate glucose homeostasis. Evans and his colleagues therefore hypothesized that treatment with rFGF1 might improve glucose metabolism. They found that acute or chronic injection of rFGF1 in genetic and dietary mouse models of type 2 diabetes normalizes blood glucose levels without affecting body weight or food intake. These effects are dependent on FGFR1 expression in adipocytes, suggesting this tissue is a key cellular target. They also show that unlike treatment with other potent insulin sensitizers, such as thiazolidinediones and FGF21, rFGF1 treatment does not result in detrimental changes in hepatic lipid profiles or bone architecture. Further, the effects of rFGF1 on metabolism were found to be independent of its mitogenic activity, suggesting the chronic benefits of rFGF1 treatment can be disassociated from any negative effects on cell proliferation, such as tumor promotion.
Although the study did not delve into mechanistic insights, the effects on glycemia were quite remarkable, and the dependence on FGFR1 suggests that development of a small-molecule activator of this receptor may be a further avenue to explore as a pharmacological agent to treat diabetes.
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Levinson, R. Diabetes: Sensitizing insulin action. Nat Med 20, 813 (2014). https://doi.org/10.1038/nm.3660