Irisin-A Pancreatic Islet Hormone

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.

Keywords: blood flow; irisin; pancreatic islets; vascular.

Figure 1

Confocal image of a single islet of Langerhans from (A–C) mouse, (D–F) rat and (G–I) human split into fibronectin type III domain-containing protein 5 (FNDC5, green), insulin (red) and a combined picture. Scale bar = 100 μm.

Figure 2

Confocal image of a single islet of Langerhans from (A–C) mouse, (D–F) rat and (G–I) human split into FNDC5 (green), glucagon (red) and a combined picture. Scale bar = 100 μm.

Figure 3

Mean irisin concentration in the effusate at the sequential perifusion of human islets with a low (3.33 mmol/L), a high (33.3 mmol/L) and a second low glucose concentration in (A) human islets (n = 7) without forskolin and (B) human islets (n = 7) with forskolin (1.0 μmol/L) at both the low and high glucose concentrations. All values are given as means ± standard error of the mean (SEM). * denotes p < 0.05 and ** p < 0.01.

Figure 4

Concentrations of insulin and glucagon in the medium after incubation with low (1.67 mmol/L) and high (16.7 mmol/L) glucose concentrations in (A,B) human islets (n = 5) and (C,D) rat islets (n = 6) in the control groups, irisin in both preincubation and incubation (24+), irisin in preincubation (24 h−), and irisin in incubation media and anti-irisin antibody, as further specified in Table 1. All irisin incubations were 100 nmol/L. All values are given as means ± SEM.

Figure 5

Total content of insulin and glucagon in islets after incubation and glucose-stimulated insulin secretion, compared between control and the two groups incubated with irisin (100 nmol/L) for 24 h in (A,B) human islets (n = 5) and (C,D) rat islets (n = 5). All values are given as means ± SEM.

Figure 6

Blood flow in rats infused for 60 min with either saline as control (black) or irisin (grey, 100 nmol/L) for (A) islet blood flow, (B) pancreatic blood flow (p = 0.074, unpaired t-test) and (C) white adipose tissue. All values are given as means ± SEM for 6 and 8 rats, in control and irisin groups, respectively. * denotes p < 0.05 and ** denotes p < 0.01 by Student’s unpaired t-test.