Irisin regulates the expression of BDNF and glycometabolism in diabetic rats.

Abstract

Irisin is a proteolytic product of the fibronectin type III domain-containing protein 5. The aim of the present study was to verify whether irisin is involved in the pathogenesis of diabetic mild cognitive impairment and elucidate the associated mechanisms. Diabetic rats were divided into four groups: Control, Model, Irisin (overexpression of irisin) and Irisin-short hairpin (sh)-RNA (irisin interference). The levels of irisin, brain-derived neurotrophic factor (BDNF), glycosylated hemoglobin A1c (GHbA1c) and advanced glycated end products (AGEs) in the serum were determined using ELISA. The expression of BDNF in the hippocampal tissue was evaluated by immunohistochemical analysis. Compared with the Control group, the levels of irisin and BDNF were markedly decreased in the Model and Irisin-shRNA groups, whereas those of GHbA1c and AGEs were markedly increased. However, the levels of irisin and BDNF in the Irisin group were significantly higher than those in the Model group, whereas the levels of GHbA1c and AGEs in the Irisin group were significantly lower. Irisin-shRNA significantly downregulated the expression of irisin and BDNF, and upregulated the levels of GHbA1c and AGEs, compared with those in the Model group. Rat primary hippocampal nerve cells were isolated and identified by microtubule-associated protein-2 labeling. The vitality of primary cells from diabetic rats, evaluated using a methyl thiazolyl tetrazolium assay, was markedly decreased and further reduced following the injection of irisin-shRNA, however, it was markedly improved following irisin treatment. The mRNA and protein levels of BDNF in the primary cells were evaluated by fluorogenic reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively, following the exposure of cells to different concentrations of glucose: 0 (control), 5.5, 15 and 25 mmol/l for 12, 24 and 48 h. The mRNA and protein expression levels of BDNF in the primary cells following exposure to glucose were significantly lower than those observed in the control. Further exposure to glucose led to a significant decrease in the expression of BDNF. In conclusion, irisin may regulate the expression of BDNF and glycometabolism in diabetic rats.