Metabolic fate of glucose in reversible low-flow ischemia of the isolated working rat heart

Bolukoglu, Hakki; Guthrie, Paul D.; Carmical, Sonya G.; Chen, T. M.; Taegtmeyer, Heinrich

doi:10.1152/ajpheart.1996.270.3.h817

Cited by 36 publications

(29 citation statements)

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“…This finding is in keeping with previous in vivo and in vitro studies that have shown that exogenous glucose continues to be incorporated in glycogen in the setting of net glycogen breakdown (3,22,23). The finding of glycogen enrichment during glycogenolysis does not support the previously proposed last on, first off degradation of myocardial glycogen (24).…”

Section: Effects Of Insulin and Acetoacetate On Glycogen Metabolismsupporting

confidence: 76%

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Russell¹,

Cline²,

Guthrie³

et al. 1997

J. Clin. Invest.

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Myocardial glucose use is regulated by competing substrates and hormonal influences. However, the interactions of these effectors on the metabolism of exogenous glucose and glucose derived from endogenous glycogen are not completely understood. In order to determine changes in exogenous glucose uptake, glucose oxidation, and glycogen enrichment, hearts were perfused with glucose (5 mM) either alone, or glucose plus insulin (40 U/ml), glucose plus acetoacetate (5 mM), or glucose plus insulin and acetoacetate, using a three tracer ( 3 H, 14 C, and 13 C) technique. Insulinstimulated glucose uptake and lactate production in the absence of acetoacetate, while acetoacetate inhibited the uptake of glucose and the oxidation of both exogenous glucose and endogenous carbohydrate. Depending on the metabolic conditions, the contribution of glycogen to carbohydrate metabolism varied from 20-60%. The addition of acetoacetate or insulin increased the incorporation of exogenous glucose into glycogen twofold, and the combination of the two had additive effects on the incorporation of glucose into glycogen. In contrast, the glycogen content was similar for the three groups. The increased incorporation of glucose in glycogen without a significant change in the glycogen content in hearts perfused with glucose, acetoacetate, and insulin suggests increased glycogen turnover. We conclude that insulin and acetoacetate regulate the incorporation of glucose into glycogen as well as the relative contributions of exogenous glucose and endogenous carbohydrate to myocardial energy metabolism by different mechanisms. ( J. Clin. Invest. 1997. 100:2892-2899.) Key words: citric acid cycle • NMR • isotopomer analysis

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Section: Effects Of Insulin and Acetoacetate On Glycogen Metabolismsupporting

confidence: 76%

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Russell¹,

Cline²,

Guthrie³

et al. 1997

J. Clin. Invest.

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“…The most wellstudied regulator of cardiac intermediary metabolism is PPARα, the transcriptional factor controlling expression of proteins involved in fatty acid uptake, transport, derivation, and oxidation [22]. PPARα signaling is impaired during hypoxia in neonatal cardiomyocytes as well as in hearts [23,24], consistent with the observation that substrate preference shifts from fatty acid to glucose utilization during myocardial ischemia [25]. With respect to other mitochondrial substrates, our understanding of the regulation of factors involved in ketone body utilization is limited, despite its use during nutrient stress.…”

Section: Preconditioning and Transcriptional Regulation Of Intermediamentioning

confidence: 63%

Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia

2007

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Myocardial ischemia, the most common cause of cardiac hypoxia in clinical medicine, occurs when oxygen delivery cannot meet myocardial metabolic requirements in the heart. This deficiency can result from either a reduced supply of oxygen (decreased coronary bloodflow) or an increased myocardial demand for oxygen (increased wall stress or afterload). Patients with stable coronary artery disease as well as patients experiencing acute myocardial infarction can experience episodes of severe ischemia. Although hypoxia is an obligatory component, it is not the sole environmental stress experienced by the ischemic heart. Reperfusion after ischemia is associated with increased oxidative stress as the heart reverts to aerobic respiration and thereby generates toxic levels of reactive oxygen species (ROS). During mild ischemia, mitochondrial function is partially compromised and substrate preferences adapt to sustain adequate ATP generation. With severe ischemia, mitochondrial function is markedly compromised and anaerobic metabolism must provide energy no matter what the cost in generation of toxic ROS adducts. Ischemia produces a variety of environmental stresses that impair cardiovascular function. As a result, multiple signaling pathways are activated in mammalian cells during ischemia/reperfusion injury in an attempt to minimize cellular injury and maintain cardiac output. Amongst the transcriptional regulators activated are members of the hypoxia inducible factor (HIF) transcription factor family. HIF factors regulate a variety of genes that affect a myriad of cellular processes including metabolism, angiogenesis, cell survival, and oxygen delivery, all of which are important in the heart. In this review, we will focus on the metabolic and angiogenic aspects of HIF biology as they relate to the heart during ischemia. We will review the metabolic requirements of the heart under normal as well as hypoxic conditions, the effects of preconditioning and its regulation as it pertains to HIF biology, the apparent roles of HIF-1 and HIF-2 in intermediary metabolism, and translational applications of HIF-1 and HIF-2 biology to cardiac angiogenesis. Increased understanding of the role of HIFs in cardiac ischemia will ultimately influence clinical cardiovascular practice.

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“…In moderate ischemia (reduction of coronary flow by 75%), glucose uptake remains unchanged, while glucose extraction increases and metabolism of glucose is directed from oxidation to lactate production. 77 In severe ischemia, myocardial glucose extraction is inversely related to coronary flow, 78 until the degree of ischemia becomes so severe that glycolysis is inhibited by the accumulation of its products. 79 Once glycolysis is inhibited, glucose uptake progressively decreases, while protons, Na ϩ , and Ca 2ϩ continue to accumulate.…”

Section: Glucose Metabolism In the Ischemic And Reperfused Heartmentioning

confidence: 99%

Glucose for the Heart

Depré¹,

Vanoverschelde²,

Taegtmeyer³

1999

Circulation

377

260

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Metabolic fate of glucose in reversible low-flow ischemia of the isolated working rat heart

Cited by 36 publications

References 0 publications

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia

Glucose for the Heart

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