Background: Diabetic nephropathy is one of the most important complications
in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic
nephropathy involve amongst others the modulation of cell signaling via AMP-activated
kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation,
and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These
processes mediate increased loss of renal cells, such as podocytes, which consequentially
leads to renal damage and loss of renal functions, such as structural integrity and glomerular
filtration in diabetic nephropathy. The anti-diabetic drug metformin has been widely
used for pharmacotherapeutic treatment of patients with diabetes mellitus. Besides its
anti-diabetic actions, recent studies revealed additional nephroprotective effects of metformin
in vitro and in vivo. Metformin was found to diminish apoptosis in different experimental
renal settings. Moreover, it was shown to reduce albuminuria in diabetic rats
as well as in patients with type 2 diabetes mellitus. These effects were demonstrated to be
mediated via the AMPK/mTOR signaling axis. These data indicate beneficial and renoprotective
effects of metformin in diabetic nephropathy.
Objective: In this review, we will summarize the latest findings regarding the nephroprotective
impact of metformin in vitro and in vivo. Moreover, we will depict and discuss the
therapeutic potential of this drug for the treatment of diabetic nephropathy.
Keywords: Metformin, hyperglycemia, diabetic nephropathy, kidney, renal damage, diabetes mellitus, podocytes,
AMP-activated protein kinase.
Rights & PermissionsPrintExport