The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Nadeem

et al. 2022

IJMS

Retinal cell death is responsible for irreversible vision loss in many retinal disorders. No commercially approved treatments are currently available to attenuate retinal cell loss and preserve vision. We seek to identify chemicals/drugs with thoroughly-studied biological functions that possess neuroprotective effects in the retina using a computational bioinformatics approach. We queried the National Center for Biotechnology Information (NCBI) to identify genes associated with retinal neuroprotection. Enrichment analysis was performed using ToppGene to identify compounds related to the identified genes. This analysis constructs a Pharmacome from multiple drug-gene interaction databases to predict compounds with statistically significant associations to genes involved in retinal neuroprotection. Compounds with known deleterious effects (e.g., asbestos, ethanol) or with no clinical indications (e.g., paraquat, ozone) were manually filtered. We identified numerous drug/chemical classes associated to multiple genes implicated in retinal neuroprotection using a systematic computational approach. Anti-diabetics, lipid-lowering medicines, and antioxidants are among the treatments anticipated by this analysis, and many of these drugs could be readily repurposed for retinal neuroprotection. Our technique serves as an unbiased tool that can be utilized in the future to lead focused preclinical and clinical investigations for complex processes such as neuroprotection, as well as a wide range of other ocular pathologies.

Section: Discussionmentioning

confidence: 99%

Using Computational Drug-Gene Analysis to Identify Novel Therapeutic Candidates for Retinal Neuroprotection

Nadeem

et al. 2022

IJMS

“…Mechanism of Action. Metformin acts by activating the adenosine monophosphate-activated protein kinase (AMPK) enzyme, which increases glucose uptake in peripheral tissues, decreasing blood glucose (Hasanvand, 2022). AMPK is an enzyme involved in the metabolism of lipids and carbohydrates.…”

Section: I) Biguanidesmentioning

confidence: 99%

A minireview of pharmacotherapy of type 2 diabetes – drugs and mechanisms

Lima

Godoy

Araújo

2022

RSD

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that originates from numerous pathogenic mechanisms, all of which result in hyperglycemia. This disease is a major cause of morbidity and mortality worldwide. Effective prevention and treatment strategies for T2DM are therefore necessary. The purpose of this review was to summarize the pharmacotherapy for patients with T2DM by discussing its pathophysiology, the therapeutic classes used in treatment strategies, as well as the mechanisms of action for each one. A literature review was conducted by searching Google Scholar, PubMed, and Science Direct databases using the search terms: type 2 diabetes mellitus, insulin, AMPK, antidiabetic drugs, incretin, SGLT2, and biguanides covering studies up to 2022. The review identified and included studies including qualitative, original research articles, and randomized controlled trial designs. The results of this study are divided into drugs that increase insulin sensitivity (e.g., biguanides, and thiazolidinediones), secretagogues (e.g., sulfonylureas, and meglitinides or glinides), incretin mimetics drugs (e.g., GLP-1 receptor agonists, and DPP-4 inhibitors), drugs that cause glycosuria (e.g., SGLT2 inhibitors), drugs that prevent glucose absorption (e.g., α-glucosidase inhibitor), and insulin. This allows the readers to understand each process while keeping the paper concise.

“…Recent research has shown that metformin not only suppresses inflammatory response by improvement of metabolic proinflammatory parameters such as hyperglycemia, hyperinsulinemia, insulin resistance, and dyslipidemia but also has a direct anti-inflammatory effect itself [21]. Numerous studies have suggested that metformin suppresses chronic inflammation by inhibiting nuclear factor-κB (NFκB) through AMPKindependent and -dependent pathways [22,23,24].…”

Section: Metformin: An Old Friend With a New Facementioning

confidence: 99%

Metformin as a Promising Anti-Aging Agent in the Treatment of Osteoarthritis

Georgiev

Kabakchieva

2022

AAEE

Osteoarthritis (OA) is traditionally considered an age-related disease. Therefore, repurposing drugs with the potential to reduce cell senescence is a justified therapeutic strategy. Such is the case of metformin, the most widely used antidiabetic medicine with well-known pharmacokinetics, acceptable toxicity, and beneficial metabolic effects. Metformin could significantly impact processes associated with aging and OA such as cellular senescence, infammaging, mitochondrial dysfunction and impaired nutrient sensing. The aim of the present narrative review is to unveil the potential of metformin to modify disease course in light of aging osteoarthritic joints. The drug has pleiotropic effects on chondrocyte and extracellular matrix metabolism and may provide through AMPK-dependent and -independent pathways a meaningful improvement of OA. Mostly preclinical and retrospective cohort studies have shown that metformin exposure could lead to the regulation of cartilage homeostasis, symptomatic relief of pain and postpone surgery for those suffering from OA. Randomized control trials are warranted to justify the preliminary expectations.