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.
Polyunsaturated Fatty Acids in Pregnancy and Metabolic Syndrome: A Review
Current Pharmaceutical Biotechnology Growth Factors in the Pathogenesis of Retinal Neurodegeneration in Diabetes Mellitus
Current Neuropharmacology Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation
Current Neurovascular Research Advances in the Generation of Functional β-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus
Current Drug Targets Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders
Current Drug Metabolism Pleiotropic Effects of PPARγ Agonist on Hemostatic Activation in Type 2 Diabetes Mellitus
Current Vascular Pharmacology Anti-diabetic Drug Metformin: Challenges and Perspectives for Cancer Therapy
Current Cancer Drug Targets Flow Cytometry Study of Leukocyte Function: Analytical Comparison of Methods and their Applicability to Clinical Research
Current Medicinal Chemistry Rheumatological Manifestations in Diabetes Mellitus
Current Diabetes Reviews Recent Advances in Synthetic Chemistry of Diabetic Research
Mini-Reviews in Medicinal Chemistry Is Metformin a Therapeutic Paradigm for Colorectal Cancer: Insight into the Molecular Pathway?
Current Drug Targets Role of Insulin Signaling in the Interaction Between Alzheimer Disease and Diabetes Mellitus: A Missing Link to Therapeutic Potential
Current Aging Science Recent Developments in the Search for Biomarkers for the Diagnosis and Monitoring of Diabetes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Under Re-organization) Role of Immune Cells in Diabetic Kidney Disease
Current Gene Therapy Molecular Remodeling of the Insulin Receptor Pathway by Thiazolidinediones in Type 2 Diabetes Mellitus: A Brief Review
Protein & Peptide Letters Inflammation, Oxidative Stress and Metabolic Syndrome: Dietary Modulation
Current Vascular Pharmacology Cyclin-Dependent Kinase 5 (Cdk5): A Potential Therapeutic Target for the Treatment of Neurodegenerative Diseases and Diabetes Mellitus
Mini-Reviews in Medicinal Chemistry Indole Alkaloids as New Leads for the Design and Development of Novel DPP-IV Inhibitors for the Treatment of Diabetes
Current Bioinformatics Toll-like Receptors and Diabetes Complications: Recent Advances
Current Diabetes Reviews Development, Optimization & Evaluation of Porous Chitosan Scaffold Formulation of Gliclazide for the Treatment of Type-2 Diabetes Mellitus
Drug Delivery Letters