# Isoflavone Protects the Renal Tissue of Diabetic Ovariectomized Rats via PPARy
## 4 Discussion  
In this work, in a model of diabetes followed by ovariectomy, we demonstrated the role of isoflavone in protecting from renal injury via PPAR-\(\gamma\). In our model, isoflavone-treated animals were protected from renal injury, observed by a reduction in the renal injury marker KIM-1 in the renal tissue. We postulate that this isoflavone-mediated protection of kidney injury occurs via PPAR-\(\gamma\), where we observed that--mainly in the model of diabetes concomitant to ovariectomy--the endometrium as much as the kidney presents a reduction in PPAR-\(\gamma\), observed at the proteinic and gene levels. Isoflavone treatment for this condition can positively modulate PPAR-\(\gamma\) at the protein and gene levels, demonstrating this possible relationship. The relationship of isoflavone with diabetes and menopause has been reviewed by numerous authors [25; 26; 27]. Induction of diabetes and ovariectomy exacerbates blood glucose [28]. In systematic reviews, there is a disparity of ideas on this. It has been reported that isoflavone can reduce the risk of type II diabetes mellitus [29; 30], but, in another systematic review, isoflavone did not significantly interfere with glucose metabolism. In further work, it has been evidenced that extracted isoflavones and those from soy protein improve the lipid profile and may prevent cardiovascular events in diabetic individuals [31]. Isoflavone and 17\(\beta\)-estradiol negatively regulate blood glucose [7; 24]. This similar effect of isoflavone or 17\(\beta\)-estradiol occurs due to estrogenic characteristics [7]. Investigations of our group have demonstrated the beneficial effect of isoflavone in ovariectomized diabetic animals [13; 14]. Above all, in this current report, we demonstrate that isoflavone shows a similar effect to 17\(\beta\)-estradiol, leading to blood glucose homeostasis, but interestingly, the isoflavone was more effective in inducing protein synthesis of PPAR-\(\gamma\) in renal tissue of diabetic animals than estrogen, and this promoted lower expression of KIM-1 in this condition. Thus, our data suggest that isoflavone was more effective in inhibiting the renal injury induced by hyperglycemia than the estrogen itself in our model. Therefore, these findings will be better explored in future studies. In animals, PPAR-\(\gamma^{-/-}\) demonstrates cross-links of glucose and lipid metabolism between adipose tissue, muscle, and liver, suggesting that PPAR\(\gamma\) is important for maintaining normal insulin sensitivity and whole-body glucose and lipid homeostasis [32]. Isoflavone is a potent agonist of PPAR\(\alpha/\gamma\) and exerts anti-inflammatory activity, which may contribute to the prevention of metabolic syndrome [33]. We have previously shown  
Figure 6: Isoflavone does not decrease glycogen storage in the actual tissue. Control (**a**), OVX (**b**), DM1 (**c**), DM1 + OVX untreated (**d**), DM1 + OVX treated with isoflavone (**e**), and DM1 + OVX treated with 17\(\beta\)-estradiol (**f**). Densiometry analysis is represented in arbitrary units (**g**). Scale bar = 50 \(\upmu\)m. Values represent mean \(\pm\) SEM (\(n=6\)). [PERSON]–[PERSON] test was performed, followed by [PERSON]’s multiple comparison test for non-normal distribution of data (\({}^{*}p<0.05\); \({}^{***}p<0.001\); \({}^{***}p<0.0001\)). in a model of renal injury by a hyper-lipidic diet that isoflavne prevents renal injury via PPAR-\(\gamma\)[14]. In this work, we demonstrated that protein loss and gene expression of PPAR-\(\gamma\) in endometrium but not in the kidney of ovariectomized diabetic animals may be related to greater kidney injury due to a greater susceptibility to glucose. Furthermore, we demonstrated through transcriptome analysis in human proximal renal tubule cells that the reduction in PPAR-\(\gamma\) expression may be glucose-concentration-dependent. Higher concentrations of glucose (i.e., 16 mM) cause an expressive decline in PPAR-\(\gamma\) expression.