Dysregulation of insulin-sensitive glucose transporters during insulin resistance-induced atrial fibrillation

Maria, Zahra; Campolo, Allison; Scherlag, Benjamin J.; Ritchey, Jerry W.; Lacombe, Véronique A.

doi:10.1016/j.bbadis.2017.12.038

Cited by 48 publications

(53 citation statements)

References 49 publications

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“…Similarly, severe hypoglycemia-induced fatal cardiac arrhythmias were enhanced in diabetic rats with insulin deficiency (14). Recently, we demonstrated that long term high-fat diet-induced insulin resistance enhanced the vulnerability of AF induction in a rodent model (15). Taken together, the results of these studies suggest that disturbances in glucose and insulin could enhance the arrhythmogenicity of the atrium, which contains the pacemaker of the heart, potentially leading to AF (6,9,16).…”

Section: Introductionmentioning

confidence: 82%

Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice

Maria

Campolo

Scherlag

et al. 2020

Front. Cardiovasc. Med.

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Diabetes has been identified as an independent risk factor for atrial fibrillation (AF), the most common chronic cardiac arrhythmia. Whether or not glucose and insulin disturbances observed during diabetes enhance arrhythmogenicity of the atria, potentially leading to AF, is not well-known. We hypothesized that insulin deficiency and impaired glucose transport provide a metabolic substrate for the development and maintenance of AF during diabetes. Transesophageal atrial pacing was used to induce AF in healthy, streptozotocin-induced insulin-deficient type 1 diabetic, and insulin-treated diabetic mice. Translocation of insulin-sensitive glucose transporters (GLUTs) to the atrial cell surface was measured using a biotinylated photolabeling assay in the perfused heart. Fibrosis and glycogen accumulation in the atrium were measured using histological analysis. Diabetic mice displayed mild hyperglycemia, increased duration and frequency of AF episodes vs. age-matched controls (e.g., AF duration: 19.7 ± 6.8 s vs. 1.8 ± 1.1 s, respectively, p = 0.032), whereas insulin-treated diabetic animals did not. The translocation of insulin-sensitive GLUT-4 and-8 to the atrial cell surface was significantly downregulated in the diabetic mice (by 67 and 79%, respectively; p ≤ 0.001), and rescued by insulin treatment. We did not observe fibrosis or glycogen accumulation in the atria of diabetic mice. Therefore, these data suggest that insulin and glucose disturbances were sufficient to induce AF susceptibility during mild diabetes.

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Section: Introductionmentioning

confidence: 82%

Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice

Maria

Campolo

Scherlag

et al. 2020

Front. Cardiovasc. Med.

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“…Maria et al reported that insulin‐resistant mice were vulnerable, and had a propensity, to both induced and spontaneous AF. In the present study, LA conduction velocity was significantly slower in the insulin‐resistant group than in the normal group.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin resistance, which is a state of decrease in insulin response, is well known to be the underlying mechanism in the development of the abnormal glucose metabolism . There are limited data about the relationship between the pathogenesis of AF and insulin resistance . In addition, it remains unclear whether insulin resistance affects AF recurrence after PVI.…”

Section: Introductionmentioning

confidence: 99%

“…9 There are limited data about the relationship between the pathogenesis of AF and insulin resistance. 10 In addition, it remains unclear whether insulin resistance affects AF recurrence after PVI. In the present study, the clinical impact of insulin resistance on the promotion of atrial remodeling and AF recurrence after PVI was investigated in patients with paroxysmal AF.…”

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confidence: 99%

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Clinical impact of insulin resistance on pulmonary vein isolation outcome in patients with paroxysmal atrial fibrillation

Hijioka

Kamioka

Matsumoto

et al. 2019

Cardiovasc electrophysiol

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Introduction The relationship between insulin resistance and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) remains unclear. Methods Drug‐refractory 114 paroxysmal AF patients (89 males, 62 ± 8 years) who underwent successful PVI were enrolled. Homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated and a value of ≥2.5 was defined as insulin resistant. The left atrial volume index (LAVI) was measured using echocardiography before and 1 year after PVI. Tumor necrosis factor‐α (TNF‐α) and TGF‐β1 serum levels were measured before PVI, and the left atrium (LA) conduction velocity was calculated. The patients were divided into two groups (group 1: HOMA‐IR < 2.5, n = 81; group 2: HOMA‐IR ≥ 2.5, n = 33). Results The LAVI between the two groups before PVI did not significantly differ (P > 0.05), nor did TNF‐α (7.7 ± 2.0 vs 7.5 ± 1.0 pg/mL; P = 0.149) or TGF‐β1 (28.4 ± 12.0 vs 27.6 ± 10.3 ng/mL; P = 0.757). LAVI before and 1 year after PVI in each group did not change. The conduction velocity of group 2 was slower than that of group 1 (0.7 ± 0.1 vs 1.1 ± 0.3 m/s, P < 0.001). Kaplan‐Meier analysis showed significantly higher AF recurrence in group 2 than that in group 1 ( P = 0.019). Cox multivariable analysis revealed that insulin resistance was an independent predictor of recurrence (hazard ratio 1.287, P = 0.004). Conclusion Our results suggest that insulin resistance promotes LA electrical remodeling and might be related to AF recurrence after PVI.

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“…Insulin resistance induces both atrial structural remodeling and abnormal intracellular calcium homeostasis, contributing to increased AF susceptibility [37]. It is reported that insulin resistance-induced AF was associated with impairment in the trafficking and expression of the major cardiac isoform GLUT4 and the novel isoform GLUT8 [38]. Inflammatory markers IL-6 and TNF play an essential role in the occurrence and development of AF.…”

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confidence: 99%

Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology

Mao

Zhang

Qiao

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Paroxysmal atrial fibrillation (AF) combined with obstructive sleep apnea hypopnea syndrome (OSAHS) is very common in clinical practice. Traditional Chinese medicine (TCM) rule of regulating the liver based on psycho-cardiology shows satisfactory effectiveness in the treatment of paroxysmal AF combined with OSAHS. However, its underlying pharmacological mechanism has not yet been elucidated. This study applied network pharmacology to identify 94 active components in the six TCM liver-regulating herbs and 182 corresponding targets from several databases and comprehensive literature studies, as well as retrieved AF combined with OSAHS-related targets. Cytoscape software was adopted to construct the component-component target network and component-putative target-AF combined with OSAHS target network. Then, we obtained 38 putative therapeutic targets against AF combined with OSAHS. After the production of a putative therapeutic target interaction network, topological analysis was adopted to determine the core targets of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. For all putative therapeutic targets, biological process analysis and pathway enrichment analysis were utilized to investigate the possible mechanism of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. Mechanistically, it included positive regulation of nitric oxide biosynthetic process, aging, response to hypoxia, TNF signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and calcium signaling pathway. Especially, six core targets of TCM liver-regulating herbs, namely, TNF, STAT3, AKT1, IL-6, TP53, and INS, were significant in the regulation of the above biological processes and pathways. This study demonstrates the multicomponent, multitarget, and multipathway feature of TCM liver-regulating herbs, provides an extensional foundation for further research, and facilitates the reasonable application of TCM liver-regulating herbs in treating paroxysmal AF combined with OSAHS.

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Dysregulation of insulin-sensitive glucose transporters during insulin resistance-induced atrial fibrillation

Cited by 48 publications

References 49 publications

Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice

Insulin Treatment Reduces Susceptibility to Atrial Fibrillation in Type 1 Diabetic Mice

Clinical impact of insulin resistance on pulmonary vein isolation outcome in patients with paroxysmal atrial fibrillation

Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology

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