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

Abstract

Background: Nephropathy is the main problem of diabetes and can be classified into several phases according to the presence of albuminuria. Adenosine monophosphate-activated protein kinase (AMPK) operates as a sensor of energy charge. Objectives: The aim of our study was to evaluate the reno-protective properties of AMPK signaling 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 received diabetic rats + metformin (DM group), and group 4 received giabetic rats + metformin + dorsomorphin (DMD group). Serum albumin, uric acid, total protein and creatinine for estimation 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 reversed by metformin administration. Our results showed that serum uric acid and creatinine were significantly increased in diabetic rats and decreased after treatment with metformin in diabetic rats. AMPK improved the histopathology and morphological changes in STZinduced diabetic rats. Administration of dorsomorphin (AMPK inhibitor) with metformin can reverse the beneficial effects of AMPK. Conclusions: AMPK signaling pathway ameliorates diabetic nephropathy by modifications of serum albumin, uric acid, total protein, creatinine and attenuation of kidney damage.

Keywords

• metformin
• creatinine
• diabetic nephropathy