Role and mechanism of cardiac insulin resistance in occurrence of heart failure caused by myocardial hypertrophy

Zheng, Liling; Li, Bingbing; Lin, Sihuang; Chen, Liangcai; Li, Hongmu

doi:10.18632/aging.102212

Cited by 28 publications

(21 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These progresses to myocardial inflammation, leading to cardiomyocyte stiffening and interstitial fibrosis, resulting in LV hypertrophy, incomplete relaxation, increasing filling pressure, and LA enlargement, which eventually causes diastolic dysfunction 55 . Second, insulin resistance plays an important role in developing diastolic dysfunction 26 . Loss of muscle mass and increased fat can exacerbate insulin resistance and reduce the availability of glucose transporter type 4.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, low skeletal muscle mass and obesity induce endothelial inflammation and insulin resistance and eventually alter myocardial structure and function, which may progress to abnormal LV diastolic function 26,27 . Thus, the presence of low skeletal muscle mass and sarcopenic obesity may contribute to diastolic dysfunction and functional decline.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults

Yoo

Park

Jun

et al. 2020

Diabetes Metabolism Res

View full text Add to dashboard Cite

BackgroundHeart failure with preserved ejection fraction is an emerging global health issue attributed to an ageing population. However, the association between low skeletal muscle mass, sarcopenic obesity, and left ventricular diastolic dysfunction remains unclear. In the current study, we aimed to investigate the relationship between low skeletal muscle mass, sarcopenic obesity, and diastolic dysfunction in a large cohort of Korean adults.MethodsWe conducted a cross‐sectional study of 31 258 subjects who underwent health examinations at Samsung Medical Centre's Health Promotion Centre in Seoul, Republic of Korea. Relative skeletal muscle mass was calculated using the skeletal muscle mass index [SMI (%) = appendicular skeletal muscle mass (kg)/body weight (kg) × 100], which was estimated by bioelectrical impedance analysis. Cardiac structure and function were evaluated by echocardiography.ResultsAmongst the 31 258 subjects, 3058 (9.78%) were determined to have diastolic dysfunction. The odds ratio (OR) of diastolic dysfunction was 1.56 [95% confidence interval (CI): 1.31‐1.85; p for trend <0.001] for the lowest SMI tertile relative to the highest SMI tertile following multivariable adjustment. Furthermore, the risk of diastolic dysfunction was much higher in the sarcopenic obesity (OR: 1.70, 95% CI: 1.44‐1.99), followed by in the obesity‐only (OR: 1.40, 95% CI: 1.21‐1.62), and sarcopenia‐only (OR: 1.32, 95% CI: 1.08‐1.61) when compared with the nonobese, nonsarcopenic group. These results remained consistent amongst the elderly (age ≥ 65 years).ConclusionsOur findings demonstrate that lower skeletal muscle mass and sarcopenic obesity are strongly associated with diastolic dysfunction in middle‐aged and older adults.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults

Yoo

Park

Jun

et al. 2020

Diabetes Metabolism Res

View full text Add to dashboard Cite

show abstract

“…IR may also alter systemic lipid metabolism and endothelial dysfunction that ultimately contribute to dyslipidemia and atherosclerotic plaque formation [ 29 , 30 ]. IR in the myocardium causes damage through a modification of the signal transduction, impaired regulation of the substrates' metabolism, and variation in the delivery of myocardium substrates [ 29 , 31 ]. These heart muscles' changes are associated with the presence of increased IR in the prediabetes patients and absent in the prediabetes-IR group.…”

Section: Discussionmentioning

confidence: 99%

“…MOR mediates the inhibitory effects of EM2, which exercises a reduced role in diabetes. Besides, poor regulation of blood glucose can lead to the attenuated effects of EM2 [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

The immune-opioid axis in prediabetes: predicting prediabetes with insulin resistance by plasma interleukin-10 and endomorphin-2 to kappa-opioid receptors ratio

Moustafa

2021

Diabetol Metab Syndr

View full text Add to dashboard Cite

Background Prediabetes is characterized by a hemoglobin A1c of 5.7–6.4% and fasting blood glucose of 100–125 mg/dl. A high percentage of prediabetes subjects develop type 2 diabetes mellitus in the next years. The effects of opioid peptides and their receptors, in addition to immunological cytokines, on prediabetes are not well understood. Therefore, molecular, physiological, and clinical studies are required to link the opioid system, immune system, and insulin resistance (IR) in prediabetes. We hypothesize that opioid peptides (endomorphin-2 (EM2), and β-endorphin (βEP)), and their receptors (µ-opioid receptors (MOR) and κ-opioid receptors (KOR)), in addition to the inflammatory cytokines (IL-6) and anti-inflammatory cytokine (IL-10), affect IR parameters in patients with prediabetes. Methods Sixty prediabetes patients with IR (prediabetes+IR) and sixty prediabetes patients without IR (prediabetes-IR), in addition to 58 controls, have participated in the study. IL-6, IL-10, EM2, βEP, MOR, and KOR were measured by the ELISA technique. Results In general, most prediabetes subjects have dyslipidemia. The IL-6, IL-10, β-endorphin, MOR, and endomorphin-2 were higher in the prediabetes subgroups than the control group. The immune system was activated in the prediabetes in an IR-dependent manner. Prediabetes+IR can be predicted by the increased levels of IL-10, βEP, and EM2 and by the combination of IL-10 and EM2/KOR with good sensitivity and specificity. Conclusion Opioid peptides and their receptors were upregulated in patients with prediabetes, depending on the significance of IR and the immune cytokines. The intercorrelation between the immune system, EOS, and insulin in prediabetes was confirmed.

show abstract

“…Glucose and fat are the main energy sources of myocardium. Insulin resistance leads to the decrease of glucose utilization, myocardial energy deficiency and cardiac dysfunction [35]. At the same time, insulin resistance is closely related to myocardial hypertrophy and myocardial fibrosis [36].…”

Section: Metabolic Abnormalities and Mitochondrial Dysfunction Are Asmentioning

confidence: 99%

Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

Li¹,

Xu²,

Mao³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Diabetic cardiomyopathy is a ventricular disease caused by diabetes mellitus. Abnormalities in the function of the glucokinase (GCK) play an important role in the development of diabetes. The present study is aimed at exploring changes in gene expression and related molecular mechanisms of diabetic myocardial injury in Gck knockout mice. Methods: Liver-specific glucokinase gene knockout mice( Gck w/- ) and wide type ( Gck w/w )mice generated using the Cre-loxP gene targeting strategy of 30- and 60-weeks of age were used in these studies. Determination of liver glucokinase enzyme activity, liver glycogen content and serum biochemistry parameters reflect the metabolic disorder in these mice. Echocardiography and surface electrocardiographs were used to evaluate cardiac function. Superoxide dismutase activity and malondialdehyde levels reflect oxidative stress in the myocardium. RNAseq, GO enrichment analysis and qPCR wereused to detect differences in the myocardial gene expression profiles of Gck w/- and Gck w/w mice. Results: Hyperglycemia and insulin resistance induced by decreased liver glucokinase expression and enzyme activity throughout the life of heterozygous Gck knockout mice do not yield body weight significant difference. However, prolonged PR interval and QRS duration, decreased left ventricular diameter and increased thickness of the posterior wall of the left ventricle were accompanied by increase of PAS and Masson positive substances in the myocardium of 60-week-old Gck knockout mice. RNAseq analysis showed that genes related tothe myosin heavy and light chains, insulin signaling pathway and oxidative phosphorylation were significantly differentially expressedbetween60-week-old Gck w/- and Gck w/w mice. Phosphorylation of AMPKβ1 and ACC in 60-week-old Gck knockout mice was decreased. Conclusions: Liver-specific Gck knock-out can induce myocardial fibrosis at an early stage and diabetic myocardial injury at alate stage. Through this process, the proportion of myosin heavy chain and light chain falls out of balance, the insulin signal pathway becomes down regulated and mitochondrial oxidative stress is up regulated, leading to myocardial disease.

show abstract

Role and mechanism of cardiac insulin resistance in occurrence of heart failure caused by myocardial hypertrophy

Cited by 28 publications

References 17 publications

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults

The immune-opioid axis in prediabetes: predicting prediabetes with insulin resistance by plasma interleukin-10 and endomorphin-2 to kappa-opioid receptors ratio

Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

Contact Info

Product

Resources

About