scholarly journals Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Maoyan Wu ◽  
Huiwen Xu ◽  
Jingyu Liu ◽  
Xiaozhen Tan ◽  
Shengrong Wan ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Therapeutic Strategies ◽  
Organ Injury ◽  
Peroxisome Proliferator ◽  
First Line ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
Line Drug ◽  
Organ Fibrosis

Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.

scholarly journals Inhibition of PPARγ by Natural Compounds as a Promising Strategy in Obesity and Diabetes

2019 ◽  
Vol 13 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Alessandra Ammazzalorso ◽  
Rosa Amoroso
Keyword(s):  
Energy Homeostasis ◽  
Natural Compounds ◽  
Peroxisome Proliferator ◽  
Clinical Role ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes ◽  
Ppar Agonists ◽  
Wide Group ◽  
Potential Use

A wide group of natural compounds (flavonoids, stilbenes, neolignans and others) has been identified as Peroxisome Proliferator-Activated Receptor (PPAR) agonists, with a large variety of chemical structure and different activity versus the three PPAR subtypes. These receptors are transcription factors controlling metabolic pathways in the organism, involved in lipid and glucose metabolism, cell differentiation and energy homeostasis. Otherwise, very little is known about natural compounds able to inhibit PPARs. A number of studies demonstrate that PPARγ repression has a beneficial effect in reducing body weight and improving insulin sensitivity, suggesting a potential clinical role in obesity and type 2 diabetes. This review analyzes natural compounds able to repress PPAR activity and their potential use in metabolic disorders.

scholarly journals PGC-1α, glucose metabolism and type 2 diabetes mellitus

2016 ◽  
Vol 229 (3) ◽  
pp. R99-R115 ◽  
Author(s):  
Haijiang Wu ◽  
Xinna Deng ◽  
Yonghong Shi ◽  
Ye Su ◽  
Jinying Wei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Therapeutic Strategies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Energy ◽  
Cellular Energy Metabolism ◽  
Shed Light

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

scholarly journals Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmad Aljada ◽  
Kshitij Ashwin Shah ◽  
Shaker A. Mousa
Keyword(s):  
Molecular Mechanisms ◽  
Review Article ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Cardiovascular Risks ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
Record Trial ◽  
Meta Analyses

Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγagonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates it with clinical and laboratory outcomes in the published literature. In addition, this review article attempts to discuss some of the molecular mechanisms regarding the association between TZDs therapy and the nontraditional cardiovascular risks.

Radioprotective effect of pioglitazone against genotoxicity induced by ionizing radiation in human healthy lymphocytes

2020 ◽  
Vol 18 ◽  
Author(s):  
Roya Kazemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Mean ◽  
Anti Inflammatory ◽  
Sensitizing Effect ◽  
Binucleated Lymphocytes ◽  
Inflammatory Effect

Objective: Pioglitazone (PG) is used to control high blood sugar in patients with type 2 diabetes mellitus. PG acts as a peroxisome proliferator-activated receptor γ agonist. In addition to the insulin-sensitizing effect, PG possesses anti-inflammatory effect. In this study, the protective effect of PG was evaluated against DNA damage induced by ionizing radiation in human healthy lymphocytes. Methods: The microtubes containing human whole blood were treated with PG at various concentrations (1-50 μM) for three hours. Then, the blood samples were irradiated with X-ray. Lymphocytes were cultured for determining the frequency of micronuclei as a genotoxicity biomarker in binucleated lymphocytes. Results: The mean percentage of micronuclei was significantly increased in human lymphocytes when were exposed to IR, while it was decreased in lymphocytes pre-treated with PG. The maximum reduction in the frequency of micronuclei in irradiated lymphocytes was observed at 5 μM of PG treatment (48% decrease). Conclusion: The anti-inflammatory property is suggested the mechanism action of PG for protection human lymphocytes against genotoxicity induced by ionizing radiation.

PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men

2005 ◽  
Vol 99 (1) ◽  
pp. 344-348 ◽  
Author(s):  
Alejandro Lucia ◽  
Félix Gómez-Gallego ◽  
Inês Barroso ◽  
Manuel Rabadán ◽  
Fernando Bandrés ◽  
...  
Keyword(s):  
Early Death ◽  
Endurance Capacity ◽  
Targeted Prevention ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Genotype Frequencies ◽  
Caucasian Men ◽  
World Class ◽  
Genetic Stratification

Animal and human data indicate a role for the peroxisome proliferator-activated receptor-γ coactivator 1α ( PPARGC1A) gene product in the development of maximal oxygen uptake (V̇o2 max), a determinant of endurance capacity, diabetes, and early death. We tested the hypothesis that the frequency of the minor Ser482 allele at the PPARGC1A locus is lower in World-class Spanish male endurance athletes (cases) [ n = 104; mean (SD) age: 26.8 (3.8) yr] than in unfit United Kingdom (UK) Caucasian male controls [ n = 100; mean (SD) age: 49.3 (8.1) yr]. In cases and controls, the Gly482Ser genotype met Hardy-Weinberg expectations ( P > 0.05 in both groups tested separately). Cases had significantly higher V̇o2 max [73.4 (5.7) vs. 29.4 ml·kg−1·min−1 (3.8); P < 0.0001] and were leaner [body mass index: 20.6 (1.5) vs. 27.6 kg/m2 (3.9); P < 0.0001] than controls. In unadjusted χ2 analyses, the frequency of the minor Ser482 allele was significantly lower in cases than in controls (29.1 vs. 40.0%; P = 0.01). To assess the possibility that genetic stratification could confound these observations, we also compared Gly482Ser genotype frequencies in Spanish ( n = 164) and UK Caucasian men ( n = 381) who were unselected for their level of fitness. In these analyses, Ser482 allele frequencies were very similar (36.9% in Spanish vs. 37.5% in UK Caucasians, P = 0.83), suggesting that confounding by genetic stratification is unlikely to explain the association between Gly482Ser genotype and endurance capacity. In summary, our data indicate a role for the Gly482Ser genotype in determining aerobic fitness. This finding has relevance from the perspective of physical performance, but it may also be informative for the targeted prevention of diseases associated with low fitness such as Type 2 diabetes.

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