Signaling steps in the induction of genomic damage by insulin in colon and kidney cells

Free Radical Biology & Medicine
Eman Maher OthmanHelga Stopper

Abstract

Diabetes mellitus (DM), a disease with almost 350 million people affected worldwide, will be the seventh leading cause of death by 2030. Diabetic patients develop various types of complications, among them an increased rate of malignancies. Studies reported the strong correlation between DM and several cancer types, of which colon and kidney cancers are the most common. Hyperinsulinemia, the high insulin blood level characteristic of early diabetes type 2, was identified as a risk factor for cancer development. In previous studies, we showed that an elevated insulin level can induce oxidative stress, resulting in DNA damage in colon cells in vitro and in kidney cells in vitro and in vivo. In the present study, we elucidate the signaling pathway of insulin-mediated genotoxicity, which is effective through oxidative stress induction in colon and kidney. The signaling mechanism is starting by phosphorylation of the insulin and insulin-like growth factor-1 receptors, followed by activation of phosphatidylinositide 3-kinase (PI3K), which in turn activates AKT. Subsequently, mitochondria and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) isoforms (Nox1 and Nox4 in colon and kidney, respectively) are activated for reactiv...Continue Reading

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Citations

Apr 22, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Changjiang YingXiaoyan Zhou
Dec 13, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eman AwadHelga Stopper
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Jul 25, 2018·European Journal of Nutrition·Tahereh SetayeshSiegfried Knasmüller
Jul 27, 2018·Scientific Reports·Ezgi Eyluel BankogluHelga Stopper
Apr 20, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Geema KodandaramanHelga Stopper
Dec 29, 2020·Frontiers in Cellular and Infection Microbiology·Yean Leng LokeSuat Cheng Peh
Feb 3, 2019·Fertility and Sterility·Mario VegaZev Williams
Jan 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuna TongYuxuan Zhu

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