Endocrine Abstracts

Background: Recent studies have demonstrated antioxidant and anti-inflammatory properties of metformin and vildagliptin, that could result in some positive effects on kidney function in diabetes. Indeed, in our previous study vildagliptin attenuated routine renal dysfunction markers in insulinopenic diabetic rats, however metformin didn’t improve it. In our current study we evaluated not only glomerular dysfunction marker (albuminuria), but also novel markers of proximal tubular injury (KIM-1, NGAL) in rats with non-genetic type 2 diabetic nephropathy treated with metformin and vildagliptin.

Methods: In 3 weeks after unilateral nephrectomy adult male Wistar rats were randomly divided into diabetic group (fed high-fat diet for 5 weeks and then successively received nicotinamide (230 mg/kg) and streptozotocin (65 mg/kg) intraperitoneally) and non-diabetic group (ND) fed with normal diet and received citrate buffer without streptozotocin. Ten weeks later, diabetic animals were divided to receive either metformin (M group) 300 mg/kg per day, either vildagliptin (V group) 8 mg/kg per day, or placebo (P group) for another 10 weeks, n=9 each.

Results: HbA1c in diabetic groups was considerably higher compare to ND (4.6±0.12%). At the end of the experiment vildagliptin treatment was able to considerably improve creatinine clearance (2.9±0.13 ml/min per kg), and reduce urinary albumin excretion ratio (21.9±1.4 mg/24 h). Even though metformin didn’t attenuate routine kidney dysfunction markers such as creatinine, creatinine clearance and albuminuria (61±2.9 μmol/l; 2.6±0.18 ml/min per kg; 25.9±4.6 mg/24 h, respectively) compared to P group (65±3.6; 2.3±0.21; 38.8±2.5, P≥0.05 each),urinary levels of KIM-1 (589±93.3 ng/ml) and NGAL (1544.9±100.6 pg/ml) in metformin-treated animals were significantly lower than that in diabetic rats without treatment (1097±91.1; 1918.6±118.1, respectively), P<0,05 each. Moreover, renoprotection in studying groups confirmed by morphological examination.

Conclusion: Thus, whereas vildagliptin treatment could attenuate routine markers of kidney injury, metformin has shown tubuloprotective properties without any effects on glomerular dysfunction in type 2 diabetic rats.