Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through activation of AMPK signaling pathway

摘要

Background: Nephropathy is the main problem of diabetes and can be classified into severalphases according to the presence of albuminuria. Adenosine monophosphate-activatedprotein kinase (AMPK) operates as a sensor of energy charge.Objectives: The aim of our study was to evaluate the reno-protective properties of AMPKsignaling pathway against streptozotocin (STZ)-induced nephropathy in the rat.Materials and Methods: Forty male Wistar rats were randomly distributed into four groups.Group 1 was normal rats (N group); group 2 was diabetic rats (D group); group 3 receiveddiabetic rats + metformin (DM group), and group 4 received giabetic rats + metformin +dorsomorphin (DMD group). Serum albumin, uric acid, total protein and creatinine forestimation of renal injury were measured. Finally, the histological study was evaluated.Results: Reduction of body weight, albumin and total protein in the diabetic rat was reversedby metformin administration. Our results showed that serum uric acid and creatinine weresignificantly increased in diabetic rats and decreased after treatment with metformin indiabetic rats. AMPK improved the histopathology and morphological changes in STZinduceddiabetic rats. Administration of dorsomorphin (AMPK inhibitor) with metformincan reverse the beneficial effects of AMPK.Conclusions: AMPK signaling pathway ameliorates diabetic nephropathy by modificationsof serum albumin, uric acid, total protein, creatinine and attenuation of kidney damage.