Glucose variability aggravates cardiac fibrosis by altering AKT signalling path

Ying, Changjiang; Liu, Ting; Ling, Hongwei; Cheng, Mingyue; Zhou, Xiaoyan; Wang, Shanshan; Mao, Yizhen; Chen, Lei; Li, Wei

doi:10.1177/1479164117698917

Cited by 46 publications

(40 citation statements)

References 43 publications

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“…Glucose oscillation induces more oxidative stress than consistent hyperglycemia, resulting in enhanced collagen synthesis and accelerated apoptosis in human umbilical vein endothelial cells ( 27 ). During periods of high glycemic variability, superoxide production via NADPH oxidase activity is induced in the mitochondria ( 28 ), and the AKT signaling pathway is inhibited by the increase in nuclear factor kappa B and caspase-3 expression ( 29 ). Therefore, overproduction of reactive oxygen species and inflammatory cytokines might cause DNA damage in the gastric mucosa and interfere with repair, exacerbating the gastric cancer risk ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study

Hong

Noh

Kim

et al. 2020

Clinical and Translational Gastroenterology

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INTRODUCTION: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM. METHODS: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements. RESULTS: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18–1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability ( P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model. DISCUSSION: In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study

Hong

Noh

Kim

et al. 2020

Clinical and Translational Gastroenterology

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“…33,34 Most recently, the involvement of the AKT pathway in this process has also been recognised. 35 Blood glucose fluctuation accelerates renal injury involving inhibition of the AKT signalling pathway in diabetic rats. 36 GV can also induce increased chromatin remodelling 37 which, can play an important role in GV-induced "metabolic memory".…”

Section: Mechanismsmentioning

confidence: 99%

Glycaemic variability in diabetes: clinical and therapeutic implications

Ceriello

Monnier

Owens

2019

The Lancet Diabetes & Endocrinology

418

342

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Glycaemic variability is an integral component of glucose homoeostasis. Although it has not yet been definitively confirmed as an independent risk factor for diabetes complications, glycaemic variability can represent the presence of excess glycaemic excursions and, consequently, the risk of hyperglycaemia or hypoglycaemia. Glycaemic variability is currently defined by a large and increasing number of metrics, representing either short-term (within-day and between-day variability) or long-term glycaemic variability, which is usually based on serial measurements of HbA or other measures of glycaemia over a longer period of time. In this Review, we discuss recent evidence examining the association between glycaemic variability and diabetes-related complications, as well as non-pharmacological and pharmacological strategies currently available to address this challenging aspect of diabetes management.

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“…For instance, in breast cancer, miR-133a regulates the cell cycle and proliferation during tumorigenesis by targeting epidermal growth factor receptor (EGFR) through the downstream molecule Akt (Cui et al, 2013 ). Similarly, numerous studies have explored the roles of Akt and Akt-related serine-threonine kinases in signaling cascades that regulate multiple activities in the heart and revealed a requirement for these proteins in the pathogenesis of cardiac fibrosis (Lin et al, 2015 ; Ying et al, 2017 ). For example, upregulation of miR-133a significantly decreased in the cardiac fibrosis by inhibiting Akt in patients and rats with chronic HF (Sang et al, 2015 ).…”

Section: The Roles Of Mir-133 In Cardiac Remodelingmentioning

confidence: 99%

miR-133: A Suppressor of Cardiac Remodeling?

Zhou

2018

Front. Pharmacol.

114

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Cardiac remodeling, which is characterized by mechanical and electrical remodeling, is a significant pathophysiological process involved in almost all forms of heart diseases. MicroRNAs (miRNAs) are a group of non-coding RNAs of 20–25 nucleotides in length that primarily regulate gene expression by promoting mRNA degradation or post-transcriptional repression in a sequence-specific manner. Three miR-133 genes have been identified in the human genome, miR-133a-1, miR-133a-2, and miR-133b, which are located on chromosomes 18, 20, and 6, respectively. These miRNAs are mainly expressed in muscle tissues and appear to repress the expression of non-muscle genes. Based on accumulating evidence, miR-133 participates in the proliferation, differentiation, survival, hypertrophic growth, and electrical conduction of cardiac cells, which are essential for cardiac fibrosis, cardiac hypertrophy, and arrhythmia. Nevertheless, the roles of miR-133 in cardiac remodeling are ambiguous, and the mechanisms are also sophisticated, involving many target genes and signaling pathways, such as RhoA, MAPK, TGFβ/Smad, and PI3K/Akt. Therefore, in this review, we summarize the critical roles of miR-133 and its potential mechanisms in cardiac remodeling.

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Glucose variability aggravates cardiac fibrosis by altering AKT signalling path

Abstract: Blood glucose variability can aggravate heart tissue fibrosis, possibly involving oxidative stress by inhibiting AKT signalling path.

Cited by 46 publications

References 43 publications

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study

Glycaemic variability in diabetes: clinical and therapeutic implications

miR-133: A Suppressor of Cardiac Remodeling?

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