A Novel Action of Insulin on Cardiac Membrane

Hiraoka, Masayasu

doi:10.1161/01.res.0000069363.30295.f9

Cited by 8 publications

(2 citation statements)

References 20 publications

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“…In addition, AT 1 receptor blockade during ischemia-reperfusion injury in rat hearts is associated with cardioprotection, increased AT 2 expression and signaling through inositol 1,4,5-trisphosphate (IP 3 ) pathway activation (22). The IP 3 pathway has also been described to be a component of insulin signaling and glucose utilization in the cardiomyocytes (11). In fact, some studies indicate that ANG II receptor activation leads to insulin resistance in vasculature through IP 3 pathway inhibition (9,18,31).…”

mentioning

confidence: 99%

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK

Molavi¹,

Chen²,

Mehta³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Molavi, Behzad, Jiawei Chen, and J. L. Mehta. Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK. Am J Physiol Heart Circ Physiol 291: H687-H693, 2006. First published March 31, 2006 doi:10.1152/ajpheart.00926.2005.-Current evidence points to renin-angiotensin system as a key mediator in ischemia-reperfusion injury. Rosiglitazone, a peroxisome proliferator-activated receptor-␥ (PPAR-␥) ligand, has recently been shown to confer cardioprotection against ischemia-reperfusion in animal models. We sought to examine the expression of ANG II receptors during PPAR-␥-mediated cardioprotection. Male Sprague-Dawley rats (nondiabetic) were fed either regular rat chow (control diet group, n ϭ 9) or rosiglitazone-rich diet (rosiglitazone-rich diet group, n ϭ 9) and were subjected to 1 h of myocardial ischemia followed by 1 h of reperfusion. A third group of rats had only thoracotomy and pericardiotomy and served as a sham control group (n ϭ 9). Hemodynamics, infarct size, and expression of ANG II type 1 and type 2 receptors (AT 1 and AT 2) were measured in all groups. There was a 58% reduction of infarct size in the rosiglitazone-rich diet group (P Ͻ 0.01 vs. control diet group). Increased myocardial expression of AT 1 receptors in the ischemic-reperfused myocardium was attenuated in the rosiglitazonerich diet group (P Ͻ 0.05 vs. control diet group). Importantly, myocardial AT 2 mRNA and protein expression were significantly increased (by Ͼ100-fold) in the rosiglitazone-rich diet group (P Ͻ 0.05). These changes were accompanied by inhibition of p42/44 MAPK in the rosiglitazone-rich diet group, while the Akt1 expression, believed to mediate insulin sensitization, remained similar in all three groups. The cardioprotective effects of rosiglitazone against myocardial ischemia-reperfusion injury are independent of its insulin-sensitizing properties and are associated with significant overexpression of AT 2 receptors along with inhibition of p42/44 MAPK. peroxisome proliferator-activated-␥ receptors; angiotensin receptors; ischemia-reperfusion injury; rosiglitazone THE IMPLEMENTATION of immediate reperfusion strategies to salvage the ischemic myocardium has reduced mortality and morbidity in the setting of acute coronary syndromes (8) but has also brought the phenomenon of ischemia-reperfusion injury into focus. This phenomenon can present clinically as acute congestive heart failure or malignant ventricular arrhythmias after successful revascularization.Previous studies have shown that ANG II type 1 (AT 1 ) receptors are overexpressed during ischemia-reperfusion and exert deleterious effects on myocardial contractility (37,38). Although a few studies have failed to show any cardioprotective effects by angiotensin receptor blockers, the bulk of current evidence suggests that AT 1 receptor blockade is associated with cardioprotection (28, 33). In addition, AT 1 receptor blockade during ischemia-reperfusion injury in rat hearts is assoc...

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confidence: 99%

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK

Molavi¹,

Chen²,

Mehta³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…TMAO and choline supplemented animals had increased heart weight to body weight ratios and cardiomyocyte fibrosys [ 23 , 24 , 150 , 253 , 254 , 263 ]. TMAO further increases the risk of heart failure by altering fuel utilization in cardiac tissue [ 264 , 265 , 266 , 267 , 268 , 269 ]. Cardiac biopsies from high fat high carbohydrate diet fed mice with elevated TMAO levels also showed increased fibrosis and inflammatory markers [ 255 ].…”

Section: Tmao Effects On Metabolic Tissuesmentioning

confidence: 99%

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

2021

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Since elevated serum levels of trimethylamine N-oxide (TMAO) were first associated with increased risk of cardiovascular disease (CVD), TMAO research among chronic diseases has grown exponentially. We now know that serum TMAO accumulation begins with dietary choline metabolism across the microbiome-liver-kidney axis, which is typically dysregulated during pathogenesis. While CVD research links TMAO to atherosclerotic mechanisms in vascular tissue, its molecular effects on metabolic tissues are unclear. Here we report the current standing of TMAO research in metabolic disease contexts across relevant tissues including the liver, kidney, brain, adipose, and muscle. Since poor blood glucose management is a hallmark of metabolic diseases, we also explore the variable TMAO effects on insulin resistance and insulin production. Among metabolic tissues, hepatic TMAO research is the most common, whereas its effects on other tissues including the insulin producing pancreatic β-cells are largely unexplored. Studies on diseases including obesity, diabetes, liver diseases, chronic kidney disease, and cognitive diseases reveal that TMAO effects are unique under pathologic conditions compared to healthy controls. We conclude that molecular TMAO effects are highly context-dependent and call for further research to clarify the deleterious and beneficial molecular effects observed in metabolic disease research.

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Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters

et al. 2006

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Cardiovascular disease is the primary cause of death in obesity and type-2 diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be involved in the development of both cardiac dysfunction and insulin resistance in these conditions. Under physiological circumstances the heart utilizes predominantly long-chain fatty acids (LCFAs) (60-70%), with the remainder covered by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of both LCFA and glucose is regulated by the sarcolemmal amount of specific transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, respectively. These transport proteins are not only present at the sarcolemma, but also in intracellular storage compartments. Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. In this review, recent findings on the insulin and contraction signalling pathways involved in substrate uptake and utilization by cardiac myocytes under physiological conditions are discussed. New insights in alterations in substrate uptake and utilization during insulin resistance and its progression towards T2DM suggest a pivotal role for substrate transporters. During the development of obesity towards T2DM alterations in cardiac lipid homeostasis were found to precede alterations in glucose homeostasis. In the early stages of T2DM, relocation of FAT/CD36 to the sarcolemma is associated with the myocardial accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin-stimulated GLUT4-translocation. These novel insights may result in new strategies for the prevention of development of cardiac dysfunction and insulin resistance in obesity and T2DM.

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A Novel Action of Insulin on Cardiac Membrane

Cited by 8 publications

References 20 publications

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters

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