Sex-Dependent Effects of Exogenous Irisin on Pancreatic Endocrine-Cell Immunophenotype in Post-Weaning Wistar Rats.

Abstract

Background/objectives: Irisin is an exercise-associated myokine with reported effects on β-cell survival, insulin secretion, and pancreatic tissue protection in experimental models of metabolic stress. However, less is known about its influence on the developing endocrine pancreas under physiological conditions. Accordingly, the aim of the present study was to determine whether exogenous recombinant FNDC5/irisin is associated with changes in pancreatic endocrine-cell immunophenotype and islet-level markers of cell turnover in male and female Wistar rats.

Methods: Thirty-two 3-week-old Wistar rats were assigned to control and irisin-treated groups, with males and females analyzed searately. Irisin was administered intraperitoneally at 100 µg/kg body weight once weekly for four weeks. Control animals received 0.9% NaCl. At the end of the experiment, serum cholesterol, fructosamine, and lipase were measured as supportive biochemical endpoints. Pancreatic sections were analyzed immunohistochemically for insulin, glucagon, somatostatin, PCNA, and cleaved caspase-3.

Results: Irisin treatment was not associated with statistically significant changes in serum cholesterol, fructosamine, or lipase. In males, irisin increased insulin immunoreactive area, insulin-positive cell percentage, and insulin-positive cell density. In females, irisin decreased glucagon immunoreactive area and glucagon-positive cell density, whereas glucagon-positive cell percentage remained unchanged. Somatostatin immunoreactive area decreased after irisin administration in both sexes, while somatostatin-positive cell percentage and density increased in males and females. PCNA-positive cell percentage decreased in both sexes after irisin treatment. Islet cleaved caspase-3 immunoreactivity, assessed as optical density, was not significantly altered.

Conclusions: Exogenous irisin modified pancreatic endocrine-cell immunophenotype in a sex- and cell-type-dependent manner in post-weaning rats. These changes occurred without significant alterations in serum lipase, fructosamine, or cholesterol and without a detectable increase in islet cleaved caspase-3 immunoreactivity under the applied analytical conditions.