ABSTRACT

OBJECTIVE

Irisin is a newly discovered peptide which is a cleaved protein derived from the full-length fibronectin type III domain containing-5 (FNDC5) that regulates energy metabolism, adipose tissue and glucose metabolism by acting as an anti-obesity and anti-diabetic hormone and it is

known that, Irisin is a Peroxisome proliferator-activated receptor-gamma [PPAR- ] Coactivator-1- alpha (PGC1- α) dependent myokine.Irisin is synthesized mainly in cardiac cells and peripheral muscles, pancreatic beta cells, liver, kidney and salivary glands.

PGC-1α is a versatile transcription cofactor that can be induced by various physiological and nutritional changes and affects glucose/fatty acid metabolism and mitochondrial functions.

In recent studies, it’s supported that dysregulation of PGC-1α involves in pathogenesis of type 2 diabetes. Transgenic mice selectively expressing PGC-1α have been described to show remarkable resistance to age-related obesity and metabolic disorders.

In addition to reducing insulin resistance and having a protective effect from diabetes, irisin has been shown to have protective effects against many cardiovascular diseases such as atherosclerosis, myocardial infarction and cardiac hypertrophy in many studies.

In this study, we examined the correlation between the vasculoprotective and cardioprotective effects of metformin and irisin levels, which have been shown to have positive effects against cell aging and insulin resistance.

METHODS

In old natural animal model that is created for 24 months, randomly selected thirty-two Wistar-Albino rats were equally divided into four groups as Group-1: Young (<12 months) control, group-2: Young+metformin, Group-3: old (>24 months) control and Group-4: old+metformin. Hearts and thoracic aorta samples were excised for analysis.

Irisin ELISA assay

Serums were obtained to determine the levels that were determined with “Rat Irisin ELİSA kit” for quantitative determination.

RESULTS

The results of the mean or median values of inflammatory and oxidative stress markers in cardiac and aortic tissues according to the groups are shown in table-1and 2.

AORTA: There was a statistically significant difference between the 4 groups in terms of irisin values (p=0.002). In post-hoc analysis, this difference was statistically significant between group-2 and group-3 (p=0.002) and group-3 and group-4 (p=0.008).

While a negative correlation (r= -0.58 ; p=0.02) was found between the Irisin and Transforming growth factor- values, a positive correlation (r= 0.52 ; p=0.04) was found between Irisin and Platelet-derived growth factor receptor-β(PDGFR-β) values.

CARDIAC: A statistically significant difference was observed between the 4 groups in terms of irisin values (p=0.000). In post-hoc analysis, this difference was statistically significant between group-2 and group-3 (p=0.000).

A positive correlation was found between the Irisin and PDGFR-β values (r= 0.59 ; p=0.02) and between Irisin and IL-6 values (r= 0.497 ; p=0.049).

CONCLUSION

In response to age-related increased inflammatory and oxidative stress, the vasculoprotective and cardioprotective effects seen in metformin groups correlate with irisin levels. Statistically significant increase in irisin levels in metformin groups supports the cell protective effects. Irisin can be evaluated in many studies as a new generation cell-protective and insulin-resistance-correcting marker.

Figure-1: Comparison of mean irisin levels