Metformin Protects against Podocyte Injury in Diabetic Kidney Disease
Abstract
:1. Introduction
2. Structure of the Nephron
3. Podocytes, the Central Components of the Glomerular Filtration Barrier
4. Diabetic Kidney Disease
4.1. Clinical Definition of DKD
4.2. Pathomorphological Characteristics of DKD
4.3. Risk Factors of DKD
4.4. Mechanisms Leading to the Development of DKD
4.4.1. Hyperglycaemia
4.4.2. Lipotoxicity and Lipid Metabolism-Associated Regulation of Podocytes
4.4.3. Chronic Low-Grade Inflammation
4.4.4. Insulin Resistance
4.4.5. Autophagy
5. Mechanisms Whereby Metformin Reduces Hyperglycaemia
6. Podocyte-Protective Mechanisms of Action of Metformin
6.1. Metformin Restores the Expression of Central Podocyte Proteins
6.2. Metformin Regulates the Dynamics of the Actin Cytoskeleton
6.3. Metformin Reduces Oxidative Stress
6.4. Metformin Ameliorates Dyslipidemia
6.5. Metformin Reduces Inflammation
6.6. Metformin Reduces Insulin Resistance
6.7. Metformin Activates Autophagy
6.8. Effects of Metformin Outside of Podocytes
7. Metformin Monotherapy and Metformin-Based Combination Therapy in T2D and DKD
7.1. Comparison of Metformin and Other Antihyperglycaemic Medications in T2D and DKD
7.2. Use of Metformin When Kidney Function Is Impaired
8. Future Perspectives
8.1. Systemic Versus Podocyte-Specific Effects of Metformin on Dyslipidemia and Inflammation
8.2. Mechanisms Whereby Metformin Reduces Insulin Resistance and Protects the Kidney and Podocytes
8.3. Metformin and Senescence of Podocytes
9. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Model | Metformin Administration | Reference |
---|---|---|
spontaneously diabetic Torii rat | 350 mg/kg daily 17 weeks | [111] |
high-fat diet and single low dose of streptozotocin rat | 150, 300 or 500 mg/kg daily 8 weeks | [112] |
high-fat diet and single low dose of streptozotocin rat | 70 mg/kg daily 13 weeks | [101] |
high-fat diet and single low dose of streptozotocin rat | 250 mg/kg daily 8 weeks | [115] |
high-fat diet and single low dose of streptozotocin rat | 150, 300 or 500 mg/kg daily 8 weeks | [132] |
streptozotocin rat | 100 or 500 mg/kg daily 8 weeks | [110] |
high-fat diet mouse | 0.5% w/w in diet 12 weeks | [118] |
db/db mouse | 200 mg/kg daily 16 weeks | [136] |
Study/Cohort | Outcome | Reference |
---|---|---|
MARCH/newly diagnosed, drug-naïve individuals with T2D (n = 762) | Reduced albuminuria | [140] |
Individuals with T2D with incipient nephropathy (switched from glybenclamide; n = 51) | Reduced albuminuria | [141] |
Individuals with uncontrolled T2D (add-on to sulfonylurea; n = 202) | Reduced albuminuria | [120] |
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Lehtonen, S. Metformin Protects against Podocyte Injury in Diabetic Kidney Disease. Pharmaceuticals 2020, 13, 452. https://doi.org/10.3390/ph13120452
Lehtonen S. Metformin Protects against Podocyte Injury in Diabetic Kidney Disease. Pharmaceuticals. 2020; 13(12):452. https://doi.org/10.3390/ph13120452
Chicago/Turabian StyleLehtonen, Sanna. 2020. "Metformin Protects against Podocyte Injury in Diabetic Kidney Disease" Pharmaceuticals 13, no. 12: 452. https://doi.org/10.3390/ph13120452