Beneficial effects of metformin on glomerular podocytes in diabetes

Rogacka, Dorota; Piwkowska, Agnieszka

doi:10.1016/j.bcp.2021.114687

Cited by 6 publications

(8 citation statements)

References 111 publications

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“…As a result, hyperglycemic-induced impairment of glucose uptake into podocytes was ameliorated [122]. These observations suggest that metformin simultaneously activates SIRT1 and AMPK and may improve the insulin responsiveness of podocytes, preventing diabetic complications [93,122].…”

mentioning

confidence: 75%

“…In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle [63]. Mature podocytes are terminally differentiated and have no regenerative capacity contrast to GEC, which potentially makes podocytes the weakest component of the glomerular filter [92,93]. For these reasons, the podocytes have become the focus of research on diabetic kidney disease in the past few years.…”

Section: Podocyte Alterations 241 Podocytes Alterations In Dkd-overviewmentioning

confidence: 99%

“…The levels of AMPK and SIRT1 are measurably decreased in the diabetic kidney animal models, which correlate with higher amounts of reactive oxygen species (ROS) and increased apoptosis, inflammation, and renal damage. Moreover, stimulation of the AMPK/SIRT1 signaling pathway is associated with protection against high glucose-induced renal injury [93].…”

mentioning

confidence: 99%

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Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis

Kleibert,

Zygmunciak,

Łakomska

et al. 2023

IJMS

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Diabetic kidney disease (DKD) is one of the leading causes of death among patients diagnosed with diabetes mellitus. Despite the growing knowledge about the pathogenesis of DKD, we still do not have effective direct pharmacotherapy. Accurate blood sugar control is essential in slowing down DKD. It seems that metformin has a positive impact on kidneys and this effect is not only mediated by its hypoglycemic action, but also by direct molecular regulation of pathways involved in DKD. The molecular mechanism of DKD is complex and we can distinguish polyol, hexosamine, PKC, and AGE pathways which play key roles in the development and progression of this disease. Each of these pathways is overactivated in a hyperglycemic environment and it seems that most of them may be regulated by metformin. In this article, we summarize the knowledge about DKD pathogenesis and the potential mechanism of the nephroprotective effect of metformin. Additionally, we describe the impact of metformin on glomerular endothelial cells and podocytes, which are harmed in DKD.

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confidence: 75%

Section: Podocyte Alterations 241 Podocytes Alterations In Dkd-overviewmentioning

confidence: 99%

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Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis

Kleibert,

Zygmunciak,

Łakomska

et al. 2023

IJMS

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“…Proximal tubule cells are part of the renal tubular system and play a critical role in reabsorbing filtered nutrients, ions, and water from the glomerular filtrate, helping to maintain the body's balance of fluids and electrolytes ( Podgórski et al, 2019 ). Dysfunction of podocytes and proximal tubules can lead to kidney diseases like diabetic nephropathy, affecting filtration and reabsorption processes, and ultimately impacting kidney function ( Rogacka and Piwkowska, 2021 ). Petrica et al examine the involvement of certain lncRNAs in tubular damage and podocyte damage in kidney disease linked with type 2 diabetes.…”

Section: Role Of Tug1 In Diabetes-associated Diseasesmentioning

confidence: 99%

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1

Ageeli Hakami

2024

Saudi Journal of Biological Sciences

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“…Indeed, pathological changes in podocyte structure and function induced by high glucose, play a role in the development of proteinuria in diabetic nephropathy. Metformin is believed to exert beneficial effects on diabetic kidney function, and a protective, AMPK-mediated action against damage in podocytes, is likely involved [ 72 ].…”

Section: Molecular Mechanisms Underlying Metformin Actionsmentioning

confidence: 99%

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

Tulipano

2021

IJMS

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Metformin is considered the first-choice drug for type 2 diabetes treatment. Actually, pleiotropic effects of metformin have been recognized, and there is evidence that this drug may have a favorable impact on health beyond its glucose-lowering activity. In summary, despite its long history, metformin is still an attractive research opportunity in the field of endocrine and metabolic diseases, age-related diseases, and cancer. To this end, its mode of action in distinct cell types is still in dispute. The aim of this work was to review the current knowledge and recent findings on the molecular mechanisms underlying the pharmacological effects of metformin in the field of metabolic and endocrine pathologies, including some endocrine tumors. Metformin is believed to act through multiple pathways that can be interconnected or work independently. Moreover, metformin effects on target tissues may be either direct or indirect, which means secondary to the actions on other tissues and consequent alterations at systemic level. Finally, as to the direct actions of metformin at cellular level, the intracellular milieu cooperates to cause differential responses to the drug between distinct cell types, despite the primary molecular targets may be the same within cells. Cellular bioenergetics can be regarded as the primary target of metformin action. Metformin can perturb the cytosolic and mitochondrial NAD/NADH ratio and the ATP/AMP ratio within cells, thus affecting enzymatic activities and metabolic and signaling pathways which depend on redox- and energy balance. In this context, the possible link between pyruvate metabolism and metformin actions is extensively discussed.

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Beneficial effects of metformin on glomerular podocytes in diabetes

Cited by 6 publications

References 111 publications

Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis

Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

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