Irisin-induced cardiac fibroblast proliferation is dependent on glucose concentration and is inhibited by WZB117

Fibroblast proliferation is influenced by inter alia the cellular transport of glucose and its metabolism. The aim of the study is to confirm whether irisin is involved in the regulation of human cardiac fibroblast proliferation, and whether its effect is dependent on glucose concentration or glucose transporter activity (GLUT1). The study also examines the expression of glucose transporters on the cardiac fibroblast cell membrane.

Human cardiac fibroblasts were cultured under hypoglycemia (1 mmol/l), normoglycemia (5 mmol/l) or hyperglycemia (25 mmol/l), and treated with different concentrations of irisin (10^- 7 M, 10^- 8 M and 10^- 9 M). The results indicate that glucose concentration had no influence on cardiac fibroblast proliferation measured by BrdU. Increased proliferation was noted at 10^- 8 M and 10^- 9 M irisin in hyperglycemia, and 10^- 9 M in normoglycemia; no such change was observed in hypoglycemia. Treatment with 10^- 8 M irisin increased glucose uptake by cardiac fibroblasts and decreased its concentration in the medium. Flow cytometry confirmed GLUT 1, 3 and 4 expression on the fibroblast surface. The GLUT 1 inhibitor WZB117 decreased fibroblast proliferation (10^- 6 M) in normoglycemic and hyperglycemic conditions, and negated the effect of irisin at 10^- 9 M. WZB117 treatment increased the glucose concentration in the culture medium.

Irisin accelerates cardiac fibroblast proliferation and glucose uptake; however, this effect is dependent on glucose concentration and GLUT1 activity. GLUT1, 3 and 4 protein expression was identified on human cardiac fibroblasts.