Editors' ChoiceDiabetes

I scream, you scream, we all scream for irisin

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Science Translational Medicine  09 Aug 2017:
Vol. 9, Issue 402, eaao2263
DOI: 10.1126/scitranslmed.aao2263


Skeletal muscle may communicate with pancreatic beta cells through irisin, a muscle-derived hormone that promotes beta cell survival and insulin release.

Irisin is a muscle-derived hormone that links exercise and glucose homeostasis and was first described in 2012. Irisin secretion from skeletal muscle results in increased energy expenditure and improved glucose tolerance. This myokine is an exciting therapeutic target for obesity and diabetes.

When insulin is released, skeletal muscle is the main tissue site for glucose uptake. Natalicchio et al. investigated whether irisin secretion allows skeletal muscle to communicate peripheral glucose needs to the endocrine pancreas, directly influencing insulin secretion. Pretreatment of insulin secreting cells with irisin protected the cells from saturated free fatty acid–induced apoptosis. These results were not replicated with treatment with monounsaturated fatty acid. The effect was replicated using serum from mice fed a high-fat diet and subsequently blocked by an irisin neutralizing antibody. Irisin pretreatment also stimulated beta cell proliferation and increased cell insulin content. Exposure of rat muscle cells to the saturated free fatty acid palmitate resulted in an acute increase in irisin secretion. In the mouse, high-fat diet resulted in an acute and sustained increase in serum irisin. Administration of exogenous irisin for 14 days increased beta cell mass, increased intracellular insulin content, and enhanced insulin secretion.

The authors conclude that irisin’s effects on insulin secretion are similar to incretins, such as Glucagon-like peptide-1. Specific free fatty acids, for example palmitate, may trigger cleavage of irisin from skeletal muscle membrane proteins. In the setting of elevated free fatty acids, such as obesity, irisin can trigger an adaptive response in the pancreas to compensate for rising insulin resistance. The beneficial effects of irisin highlight the need to identify the missing link: the irisin receptor.

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