Metformin, widely used for treatment of type 2 diabetes, inhibits mitochondrial respiratory chain complex and transiently decreases mitochondrial energy production. This energetic stress increases intracellular AMP level, leading to AMP-activated protein kinase (AMPK) activation. AMPK is a metabolic sensor and has several beneficial effects on intracellular homeostasis, such as regulating glycolysis and lipid metabolism. As shown by various lines of evidence, AMPK activation is important for the beneficial effect of metformin on type 2 diabetes treatment.
In addition to diabetic-associated diseases, several studies have reported that metformin ameliorates tumor progression, inflammatory disease, and tissue fibrosis. Considering its relatively low cost and safety, metformin is useful not only for diabetes-related diseases but also for non-diabetic diseases.
In a recently published study report, researchers have highlighted that metformin significantly prolongs the survival of mice in a model that simulates the pathology of non-diabetic chronic kidney disease (ND-CKD) by ameliorating pathological conditions like reduced kidney function, glomerular damage, inflammation and fibrosis. The findings have been published in Scientific Reports.
Metformin is widely used for the treatment of type 2 diabetes, and increasing numbers of studies have shown that metformin also ameliorates tumor progression, inflammatory disease, and fibrosis. However, the ability of metformin to improve non-diabetic glomerular disease and chronic kidney disease (CKD) has not been explored.
With this in mind, researchers undertook the recent study to investigate the effect of metformin on non-diabetic glomerular disease, where they used a mouse model of Alport syndrome (Col4a5 G5X) which were treated with metformin or losartan, used as a control treatment. The team also investigated the effect of metformin on adriamycin-induced glomerulosclerosis model.
Data analysis brought forth some key facts.
Pathological and biochemical analysis showed that metformin or losartan suppressed proteinuria, renal inflammation, fibrosis, and glomerular injury and extended the lifespan in Alport syndrome mice.
Transcriptome analysis showed that metformin and losartan influenced molecular pathways-related to metabolism and inflammation. Metformin altered multiple genes including metabolic genes not affected by losartan.
Metformin also suppressed proteinuria and glomerular injury in the adriamycin-induced glomerulosclerosis mouse model.
Results showed that metformin ameliorates the glomerular sclerosis and CKD phenotype in non-diabetic chronic glomerular diseases.
Metformin may have therapeutic potential for not only diabetic nephropathy but also non-diabetic glomerular disease including Alport syndrome.
For full article follow the link: 10.1038/s41598-021-86109-1
Primary source: Scientific Reports