Abstract
Irisin is a myokine involved in glucose homeostasis. It is primarily expressed in skeletal muscle, but also in the pancreas. This study aimed to elucidate its presence and role in the islets of Langerhans—i.e., its effect on insulin and glucagon secretion as well as on blood flow in the pancreas. The precursor of irisin, fibronectin type III domain-containing protein 5 (FNDC5), was identified in rat and human islets by both qPCR and immunohistochemistry. Both α- and β-cells stained positive for FNDC5. In human islets, we found that irisin was secreted in a glucose-dependent manner. Neither irisin nor an irisin-neutralizing antibody affected insulin or glucagon secretion from human or rat islets in vitro. The insulin and glucagon content in islets was not altered by irisin. The intravenous infusion of irisin in Sprague Dawley rats resulted in nearly 50% reduction in islet blood flow compared to the control. We conclude that irisin is an islet hormone that has a novel role in pancreatic islet physiology, exerting local vascular effects by diminishing islet blood flow without affecting insulin secretion per se.
Highlights
Irisin is a myokine related to exercise that was first discovered as a secreted peptide in mouse skeletal muscle in 2012
We found that irisin was secreted in a glucose-dependent manner
We conclude that irisin is an islet hormone that has a novel role in pancreatic islet physiology, exerting local vascular effects by diminishing islet blood flow without affecting insulin secretion per se
Summary
Irisin is a myokine related to exercise that was first discovered as a secreted peptide in mouse skeletal muscle in 2012. It is cleaved from its precursor fibronectin type III domaincontaining protein 5 (FNDC5) [1]. Irisin is known to increase the expression of mitochondrial uncoupling protein 1, converting white adipose tissue (WAT) into brown-like adipose tissue [2,3]. The net effect is weight reduction and improved glucose metabolism [1,4]. Irisin holds the potential to reverse obesity. Induced modest weight reduction as well as lowered insulin and glucose levels in obese high-fat diet mice have, consistent with this, been reported previously [1]
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