Background: Diabetic nephropathy (DN) is the most common cause of end stage renal disease (ESRD), and the leading cause of death in diabetic patients. Treatment with thiazolidinediones, particularly pioglitazone, may ameliorate kidney deterioration. Moreover, several peptide hormones participate in maintaining metabolic homeostasis including the recently discovered adropin. Data regarding adropin-circulating levels in type II diabetes mellitus (T2DM) are still conflicting.
Objective: This study was designed to determine pioglitazone effect on some metabolic and kidney function parameters in type II diabetic rat model, and to investigate the relationship between serum adropin and such parameters.
Materials and methods: Thirty healthy adult male albino rats were used for this study. The rats were randomly and equally divided into three groups. Group-1; control group, group-2; type II diabetic group, and group-3; pioglitazone- treated diabetic group. Rats were examined for body weight, body mass index (BMI), adropin, glucose & insulin, insulin resistance (HOMA-IR), lipids profile, inflammatory cytokines [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1)], serum urea, creatinine, uric acid, angiotensin II, mean arterial blood pressure (MABP), urine flow rate, protein, creatinine, glomerular filtration rate (GFR), renal malondialdhyde (MDA) level, glutathione peroxidase (GSH‑Px), and superoxide dismutase (SOD) activities. Histopathological examinations for kidney tissues were also done.
Results: The present study revealed that diabetic rats showed significantly lower serum adropin levels than controls. Diabetes also significantly increased serum glucose with insulin resistance, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c), serum IL-6, TNF-α, PAI-1, serum urea, creatinine, uric acid, angiotensin II , MABP, urine flow rate, protein and renal MDA [with significant negative correlation versus serum adropin] but significantly decreased serum insulin and high density lipoprotein-cholesterol (HDL-c), urine creatinine, GFR and renal SOD & GSH‑Px activities [with significant positive correlation versus serum adropin] together with deterioration of kidney histoarchitecture. Moreover, pioglitazon treatment resulted in a significant recovery in the above mentioned parameters in the treated diabetic group.
Conclusion: Serum adropin concentration was negatively associated with the observed renal deterioration and may have a potential protective role, in addition to pioglitazone ameliorating effects, in diabetic nephropathy.