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Pleiotropic effects of metformin on inflammation, oxidative and dicarbonyl stress in transgenic spontaneously hypertensive rats expressing human C-reactive protein.


ABSTRACT: Inflammation, oxidative and dicarbonyl stress play important roles in the pathophysiology of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver, however, its “pleiotropic“ effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP). In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL6 while levels of human CRP remained unchanged and metformin also significantly reduced oxidative stress (levels of conjugated dienes and TBARS) in the liver while no significant effects were observed in SHR control rats. In addition, in the presence of high human CRP, metformin reduced methylglyoxal levels in left ventricles but not in kidneys. Finally, metformin treatment reduced adipose tissue lipolysis. Possible molecular mechanisms of metformin action studied by gene expression profiling in the liver revealed deregulated genes from inflammatory, insulin signaling, AMP-activated protein kinase (AMPK) signaling and gluconeogenesis pathways. It can be concluded that in the presence of high levels of human CRP metformin protects against inflammation, oxidative and dicarbonyl stress in the heart and ameliorates insulin resistance and dyslipidemia.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Olena Oliyarnyk 

PROVIDER: E-MTAB-3791 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

Malínská Hana H   Oliyarnyk Olena O   Škop Vojtěch V   Šilhavý Jan J   Landa Vladimír V   Zídek Václav V   Mlejnek Petr P   Šimáková Miroslava M   Strnad Hynek H   Kazdová Ludmila L   Pravenec Michal M  

PloS one 20160310 3


Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hype  ...[more]

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