Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats

Abstract

Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.

Metformin attenuates renal medullary hypoxia in diabetic nephropathy through inhibition uncoupling protein‐2

“…However, the present study measured GFR directly by clearance of inulin and estimated filtration barrier integrity from urinary excretion of albumin in order to avoid the commonly acknowledged problems associated with tubular handling of creatinine in rodents . Importantly, previous studies have reported beneficial effects of metformin on DKD when treating for 8 to 13 weeks after the onset of diabetes . In the present study, we investigated the effect of metformin on intrarenal oxygen availability already after 4 weeks of diabetes duration, since we hypothesize that early changes in kidney oxygen metabolism is a crucial component for the onset and progression of DKD.…”

“…33 Importantly, previous studies have reported beneficial effects of metformin on DKD when treating for 8 to 13 weeks after the onset of diabetes. 21,34 In the present study, we investigated the effect of metformin on intrarenal oxygen availability already after 4 weeks of diabetes duration, since we hypothesize that early changes in kidney oxygen metabolism is a crucial component for the onset and progression of DKD.…”

SHIPping out diabetes—Metformin, an old friend among new SHIP2 inhibitors

“…Various mechanisms have been proposed. In rats with T2D, metformin increases the expression of nephrin and podocalyxin, both known to be downregulated or mislocalized in DKD . Treatment of primary rat podocytes with metformin activates protein deacetylase sirtuin 1 (SIRT1) and AMPK, and prevents high glucose‐induced downregulation of SIRT1 expression .…”

Ренопротекторний Ефект Метформіну В Щурів Із Цукровим Діабетом 2-Го Типу Реалізується Шляхом Посилення Експресії Фактора Пігментного Епітелію В Тканині Нирок

“…We followed the experimental methods of Ye et al (2015) [9]. Forty-four male SD rats (180-200 g, SPF grade) aged 8 weeks were purchased from the Experimental Animal Center of Anhui Medical University (Anhui, China).…”