Interrelationship between lactate and cardiac fatty acid metabolism

Vusse, Ger J.; Groot, M.J.M. de

doi:10.1007/bf01270563

Cited by 32 publications

(12 citation statements)

References 42 publications

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“…However, energy substrate preference is dynamic to fulfill the energetic requirements of one of the most metabolically active organs in the body. Substrate utilization in the myocardium is dependent on vascular perfusion, energy demand, substrate availability, and local/systemic hormonal changes (128,215). For example, the heart preferentially shifts toward glucose rather than fatty acid or lactate metabolism under ischemic conditions (128).…”

Section: Myocardial Metabolic Signalingmentioning

confidence: 99%

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Cooper

Whaley‐Connell²,

Habibi³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

261

230

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JR. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol 293: H2009 -H2023, 2007. First published June 22, 2007; doi:10.1152/ajpheart.00522.2007.-Hypertension commonly occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome. Insulin resistance plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease. There is accumulating evidence that insulin resistance occurs in cardiovascular and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue). Activation of the renin-angiotensin-aldosterone system and subsequent elevations in angiotensin II and aldosterone, as seen in cardiometabolic syndrome, contribute to altered insulin/ IGF-1 signaling pathways and reactive oxygen species formation to induce endothelial dysfunction and cardiovascular disease. This review examines currently understood mechanisms underlying the development of resistance to the metabolic actions of insulin in cardiovascular as well as skeletal muscle tissue.HYPERTENSION is present in ϳ30% of the adult United States population and often occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome (CMS) (29,115,163,186,190). According to recent data, up to 70 million Americans have insulin resistance, which plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease (CKD), and cardiovascular (CV) disease (CVD) (69). There is accumulating evidence that insulin resistance occurs in CV and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue) (125,186,190). This review focuses on currently accepted mechanisms underlying the development of resistance to the metabolic actions of insulin in CV tissue (see Figs. 1 and 2) as well as skeletal muscle tissues (27,190) (see Fig. 3). Normal Actions of Insulin in CV TissueBoth insulin and IGF-1 receptors exist in CV tissue (186). Upon binding to specific receptors, they activate a number of downstream signaling systems that result in vasorelaxation (125, 188 -191) and myocardial glucose uptake and alteration of cardiac energy homeostasis (125,186,190). Activation of the insulin receptor (IR) and IGF-1 receptor, ligand-activated transmembrane receptors with tyrosine kinase activity, phosphorylates intracellular substrates including IR substrate (IRS) family members and Shc, which, in turn, serve as docking proteins for downstream signaling molecules (27,125). IRS phosphorylation of tyrosine moieties results in the engagement of Src homology 2 (SH2) domain-binding motifs for SH2 domain signaling molecules, including phosphatidyl 3-kinase (PI3K) and Grb-2. When SH2 domains of the p85 regulatory subunit bind to tyrosine-phosphorylated motifs on IRS-1, this activates the preassociated p110 catalytic subunit to generate phosph...

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Section: Myocardial Metabolic Signalingmentioning

confidence: 99%

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Cooper

Whaley‐Connell²,

Habibi³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

261

230

View full text Add to dashboard Cite

show abstract

“…Under in vivo conditions, the majority of lactate taken up by the heart is subsequently oxidized (2,19) and thus represents a significant source of energy for the heart (2,17,48,52). In light of the importance of lactate for myocardial energy production, an increasing number of investigators are now including both glucose and lactate as substrates in ex vivo perfusion studies of the regulation of cardiac metabolism (1,13,20,40).…”

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confidence: 99%

Evidence of separate pathways for lactate uptake and release by the perfused rat heart

Chatham

Rosiers

Forder

2001

American Journal of Physiology-Endocrinology and Metabolism

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The simultaneous release and uptake of lactate by the heart has been observed both in vivo and ex vivo; however, the pathways underlying these observations have not been satisfactorily explained. Consequently, the purpose of this study was to test the hypothesis that hearts release lactate from glycolysis while simultaneously taking up exogenous lactate. Therefore, we determined the effects of fatty acids and diabetes on the regulation of lactate uptake and release. Hearts from control and 1-wk diabetic animals were perfused with 5 mM glucose, 0.5 mM [3-(13)C]lactate, and 0, 0.1, 0.32, or 1.0 mM palmitate. Parameters measured include perfusate lactate concentrations, fractional enrichment, and coronary flow rates, which enabled the simultaneous, but independent, measurements of the rates of 1) uptake of exogenous [(13)C]lactate and 2) efflux of unlabeled lactate from metabolism of glucose. Although the rates of lactate uptake and efflux were both similarly inhibited by the addition of palmitate, (i.e., the ratio of lactate uptake to efflux remained constant), the ratio of lactate uptake to efflux was significantly higher in the controls compared with the diabetic group (1.00 +/- 0.14 vs. 0.50 +/- 0.07, P < 0.002). These data, combined with heterogeneous (13)C enrichment of tissue lactate, pyruvate, and alanine, suggest that glycolytically derived lactate production and oxidation of exogenous lactate operate as functionally separate metabolic pathways. These results are consistent with the concept of an intracellular lactate shuttle.

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“…Indeed, carbohydrates such as lactate and pyruvate represent a significant source of energy for the heart; the precise contribution is very sensitive to changes in substrate availability, hormonal milieu and disease [13][14][15][16][17][18][19]. The situation becomes even more complex when one considers the intriguing observation that has been repeatedly reported in both in vivo and ex vivo heart studies, that where there is oxidation of exogenous lactate, there is also a simultaneous efflux of lactate originating from the metabolism of exogenous glucose [13,14,18,[20][21][22].…”

Section: Probing the Role And Regulation Of Complex Metabolic Networkmentioning

confidence: 93%

Myocardial phenotyping using isotopomer analysis of metabolic fluxes

Rosiers

Chatham

2005

Biochemical Society Transactions

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Over the past 20 years, stable isotopes combined with isotopomer analysis have proven to be a powerful approach to probe the dynamics of metabolism in various biological systems, including the heart. The aim of this paper is to demonstrate how isotopomer analysis of metabolic fluxes can provide novel insights into the myocardial phenotype. Specifically, building on our past experience using NMR spectroscopy and GC-MS as applied to investigations of cardiac energy metabolism, we highlight specific complex metabolic networks that would not be predicted by classical biochemistry or by static measurements of metabolite, protein and mRNA levels.

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Interrelationship between lactate and cardiac fatty acid metabolism

Cited by 32 publications

References 42 publications

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Evidence of separate pathways for lactate uptake and release by the perfused rat heart

Myocardial phenotyping using isotopomer analysis of metabolic fluxes

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