Impairment of glucose metabolism and energy transfer in the rat heart

Carvajal, Karla; Baños, Guadalupe; Moreno‐Sánchez, Rafael

doi:10.1007/978-1-4419-9236-9_20

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…Akt-interacting proteins with diminished abundance in MetS. The PI3K/Akt pathway has a critical role in glucose metabolism, and the dysregulation of glucose uptake and oxidation in the heart of sucrose-fed rats has already been described [55]. The diminished interaction of Akt with energy metabolism-related proteins found in our study further emphasizes the relevance of this process in MetS and the critical role of Akt in heart metabolism.…”

Section: Redistribution Of Akt-interacting Proteins In Mets Cardiomyosupporting

confidence: 79%

“…It has been reported that insulin induces Akt interaction with pyruvate dehydrogenase (PDH) complex in mitochondria, and this interaction up-regulates PDH enzymatic activity in cardiomyocytes [58]. Interestingly, Carvajal et al [55], using a similar experimental model to ours, reported a diminished level of cardiac PDH in its active form. In agreement with those results, we found a diminished abundance of PDH in complex with Akt in MetS cardiomyocytes.…”

Section: Redistribution Of Akt-interacting Proteins In Mets Cardiomyosupporting

confidence: 57%

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Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes

et al. 2020

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Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, with insulin resistance as a critical component for its development. Insulin signaling in the heart leads to Akt (also known as PKB) activation, a serine/threonine protein kinase, which regulates cardiac glucose metabolism and growth. Cardiac metabolic inflexibility, characterized by impaired insulin-induced glucose uptake and oxidation, has been reported as an early and consistent change in the heart of different models of MetS and diabetes; however, the evaluation of Akt activation has yielded variable results. Here we report in cardiomyocytes of MetS rats, diminished insulin-induced glucose uptake and Akt activation, evaluated by its impaired mobilization towards the plasma membrane and phosphorylation, and reflected in a redistribution of its interacting proteins, assessed by label-free mass spectrometry (data are available via ProteomeXchange with identifier PXD013260). We report 45 proteins with diminished abundance in Akt complex of MetS cardiomyocytes, mainly represented by energy metabolism-related proteins, and also, 31 Akt-interacting proteins with increased abundance, which were mainly related to contraction, endoplasmic reticulum stress, and Akt negative regulation. These results emphasize the relevance of Akt in the regulation of energy metabolism in the heart and highlight Akt-interacting proteins that could be involved in the detrimental effects of MetS in the heart.

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Section: Redistribution Of Akt-interacting Proteins In Mets Cardiomyosupporting

confidence: 79%

Section: Redistribution Of Akt-interacting Proteins In Mets Cardiomyosupporting

confidence: 57%

Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes

et al. 2020

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“…Taken together, these results suggest a pivotal role of CaMKII in the progression of prediabetic cardiomyopathy. At early stages of MetS, when heart energy demand is still not compromised, CaMKII is upregulated; while at late stages of MetS, with marked diminution of ATP, phosphocreatine content; and creatine kinase activity [61], CaMKII is downregulated [18].…”

Section: Discussionmentioning

confidence: 99%

Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats

et al. 2020

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“…Our results revealed a significant decrease in Ca 2+ spark frequency and amplitude, reducing the diastolic Ca 2+ leak in MetS cells (Figure 2); this suggests reduced RyR recruitment or activation (Hoang-Trong et al, 2015). Sucrose-fed rat hearts have a marked diminution of ATP and phosphocreatine content and creatine kinase activity (Carvajal et al, 2003). Because diastolic Ca 2+ leak is energetically costly, the finding of a significant reduction of this parameter in MetS cardiomyocytes is not surprising, though it is in disagreement with other reports in insulin-resistant rats (Okatan et al, 2016; Sommese et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats

et al. 2019

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Metabolic syndrome (MetS) has become a global epidemic. MetS is a serious health problem because of its related cardiovascular complications, which include hypertension and delayed heart rate recovery after exercise. The molecular bases of cardiac dysfunction in MetS are still under scrutiny and may be related to anomalies in the activity and expression of key proteins involved in the cardiac excitation–contraction coupling (ECC). The cardiac Ca 2+ channel/ryanodine receptor (RyR2) participates in releasing Ca 2+ from internal stores and plays a key role in the modulation of ECC. We examined alterations in expression, phosphorylation status, Ca 2+ sensitivity, and in situ function (by measuring Ca 2+ sparks and Ca 2+ transients) of RyR2; alterations in these characteristics could help to explain the Ca 2+ handling disturbances in MetS cardiomyocytes. MetS was induced in rats by adding commercially refined sugar (30% sucrose) to their drinking water for 24 weeks. Cardiomyocytes of MetS rats displayed decreased Ca 2+ transient amplitude and cell contractility at all stimulation frequencies. Quiescent MetS cardiomyocytes showed a decrease in Ca 2+ spark frequency, amplitude, and spark-mediated Ca 2+ leak. The [ 3 H]-ryanodine binding data showed that functionally active RyRs are significantly diminished in MetS heart microsomes; and exhibited rapid Ca 2+ -induced inactivation. The phosphorylation of corresponding Ser2814 (a preferential target for CaMKII) of the hRyR2 was significantly diminished. RyR2 protein expression and Ser2808 phosphorylation level were both unchanged. Further, we demonstrated that cardiomyocyte Ca 2+ mishandling was associated with reduced SERCA pump activity due to decreased Thr17-PLN phosphorylation, suggesting a downregulation of CaMKII in MetS hearts, though the SR Ca 2+ load remained unchanged. The reduction in the phosphorylation level of RyR2 at Ser2814 decreases RyR2 availability for activation during ECC. In conclusion, the impaired in situ activity of RyR2 may also account for the poor overall cardiac outcome reported in MetS patients; hence, the SERCA pump and RyR2 are both attractive potential targets for future therapies.

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Impairment of glucose metabolism and energy transfer in the rat heart

Cited by 8 publications

References 52 publications

Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes

Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes

Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats

Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats

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