Inhibition of glucose transport by cyclic GMP in cardiomyocytes

Bergemann, Christian; Löken, Christiane; Becker, Christoph; Graf, Bettina; Hamidizadeh, Masoumeh; Fischer, Yvan

doi:10.1016/s0024-3205(01)01222-x

Cited by 18 publications

(12 citation statements)

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“…The pH; concentrations of oxygen; and total as well as isotope-labeled FFA, lactate, and glucose and 3 H-oleate, 3 H 2 O, and 14 CO 2 were measured in arterial and cardiac venous blood samples as described (6,25,26) to calculate myocardial oxygen consumption (MVO 2 ) and the rates of substrate uptake and oxidation in the LAD territory. To measure O 2 delivery to ischemic tissue, arterial oxygen content was multiplied by microsphere-calculated absolute flow at baseline and at 45 min of ischemia.…”

Section: Methodsmentioning

confidence: 99%

“…Exogenous NO, by means of its second messenger cGMP, inhibits glucose uptake and utilization in ischemic (1) as well as nonischemic isolated hearts (2) and in quiescent myocytes (3). Endogenous NO is likely to be responsible for a tonic inhibition of cardiac carbohydrate metabolism, as indicated by the marked elevation of glucose uptake, under basal conditions, in isolated hearts from endothelial NO synthase (NOS) knockout mice (4).…”

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confidence: 99%

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Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

Lei

Matsuo

Labinskyy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although the underlying mechanism(s) and functional consequences of this effect are not clearly understood. We tested the hypothesis that NO inhibits the activation of AMP-activated protein kinase (AMPK) and translocation of cardiac glucose transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced in open-chest dogs by a 66% flow reduction in the left anterior descending coronary artery (LAD). During ischemia, dogs were untreated (control) or treated by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 g⅐kg ؊1 ⅐min ؊1 ); (ii) 8-Br-cGMP (50 g⅐kg ؊1 ⅐min ؊1 ); or (iii) NO synthase inhibitor L-nitro-argininemethylester (40 g⅐kg ؊1 ⅐min ؊1 ; n ‫؍‬ 9 per group). Cardiac substrate oxidation was measured with isotopic tracers. There were no differences in myocardial blood flow or oxygen delivery among groups; however, at 45 min of ischemia, the activation of AMPK was significantly less in NTG (77 ؎ 12% vs. nonischemic myocardium) and 8-Br-cGMP (104 ؎ 13%), compared with control (167 ؎ 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 ؎ 7%) and 8-Br-cGMP (120 ؎ 11%), compared with control (165 ؎ 17%). Glucose uptake and lactate output were 30% and 60% lower in NTG compared with control. Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and glucose uptake. Contractile function in the ischemic region was significantly improved by NTG and L-nitro-argininemethylester. In conclusion, in ischemic myocardium an NO donor inhibits glucose uptake and lactate production via a reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of metabolic modulation and myocardial protection activated by NO donors.heart ͉ ischemia ͉ metabolism N itric oxide (NO) affects myocardial substrate utilization, exerting an inhibitory action on myocardial glucose uptake and metabolism, although the underlying mechanisms and functional implications of this effect, in vivo, remain poorly understood. Exogenous NO, by means of its second messenger cGMP, inhibits glucose uptake and utilization in ischemic (1) as well as nonischemic isolated hearts (2) and in quiescent myocytes (3). Endogenous NO is likely to be responsible for a tonic inhibition of cardiac carbohydrate metabolism, as indicated by the marked elevation of glucose uptake, under basal conditions, in isolated hearts from endothelial NO synthase (NOS) knockout mice (4). This effect is not peculiar to in vitro preparations, because NOS blockade enhances cardiac glucose uptake and oxidation and reduces free fatty acid (FFA) utilization in conscious dogs (5, 6). Notably, NO synthesis increases in ischemic myocardium (7,8); however, the metabolic effects of endogenous NO under this pathological condition remain unclear.During ischemia, glucose uptake and glycolytic flux are markedly accelerated and assume a critical role in preserving myocyte function (9-...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

Lei

Matsuo

Labinskyy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…In adipocytes, which had been permeabilized to allow the cellular entry of non-permeant nucleoside phosphates, the increase in Rab activity upon GTPγS addition induces the translocation of GLUT4 to the plasma membrane in an insulin-like manner [3]. These findings have been confirmed in permeabilized cardiac myocytes [5].…”

Section: Glut4 and Insulinmentioning

confidence: 97%

“…In addition all of them have proven successful in stimulating glucose uptake and GLUT4 translocation (Fig. 3, see also [5,31,127]). However, only oligomycin enhances FA uptake, whereas DNP and rotenone inhibit this process rather substantially (Fig.…”

Section: Regulation By Contractionmentioning

confidence: 97%

Regulation of cardiac long-chain fatty acid and glucose uptake by translocation of substrate transporters

Luiken

Coort

Koonen

et al. 2004

Pflugers Arch - Eur J Physiol

152

103

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Cardiac uptake of long-chain fatty acids (FA) is mediated predominantly by two membrane-associated proteins, the 43-kDa plasma membrane fatty acid-binding protein (FABPpm) and the 88-kDa fatty acid translocase/CD36 (FAT/CD36). While FABPpm is present constitutively in the sarcolemma, FAT/CD36 is recycled between an intracellular membrane compartment and the sarcolemma. Since the amount of sarcolemmal FAT/CD36 is a major determinant of cellular FA uptake, understanding of the regulation of its recycling is likely to provide new insights into altering substrate preference of the heart. FAT/CD36 recycling displays a remarkable similarity with that of the two glucose transporters (GLUT) in the heart, GLUT1 and GLUT4. Translocation of all three transporters is induced by insulin and by contraction, which stimuli activate distinct signalling cascades. The insulin pathway involves phosphatidylinositol-3 kinase (PI3K) whilst the contraction pathway is dependent on AMP-activated protein kinase (AMPK). For the identification of additional protein components involved in the regulation of FAT/CD36 recycling, valuable lessons can be learned from GLUT1 and GLUT4 recycling. Especially GLUT4 recycling is an intensively studied process in which a number of signalling proteins, both upstream and downstream from PI3 K and AMPK, have been identified, as well as proteins that are part of the translocation machinery involving Rab GTPases and soluble N-ethylmaleimide attachment protein receptors (SNAREs). Comparison of the magnitude of the effects of insulin and contraction on substrate uptake and on transporter appearance in the sarcolemma have revealed that FAT/CD36 recycling resembles GLUT1 recycling more closely than that of GLUT4. This pinpoints the recycling compartment and excludes a pre-endosomal storage compartment as the intracellular storage site for FAT/CD36. Further research will probably establish whether FAT/CD36 translocation is (partly) coupled to that of one or both GLUTs or, alternatively, whether it is a distinct process that also can be induced independently of GLUT1 or GLUT4 movement. In the latter case, a unique set of proteins would be dedicated to FAT/CD36 recycling, which would then provide an attractive target for manipulating cardiac substrate preference.

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“…YC-1 has been shown to robustly inhibit growth of VSMCs [46,62] and vascular endothelial cells [72], both in primary cultures and whole animal models, as well as modulate levels of vascular cell apoptosis [73,74]. In diabetes, YC-1 serves to inhibit glucose transport in cardiac myocytes through sGC/cGMP-dependent mechanisms [75]. Further details of these findings are available in a comprehensive prior review by this group [55].…”

Section: Heme-dependent Sgc Stimulators a Yc-1mentioning

confidence: 99%

Pharmacologic Modulators of Soluble Guanylate Cyclase/Cyclic Guanosine Monophosphate in the Vascular System - From Bench Top to Bedside

Jackson¹,

Mukhopadhyay²,

Tulis³

2007

curr vasc pharmacol

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Guanosine-dependent cyclic nucleotide second messenger signaling has been implicated as a pivotal mediator of vascular function under both homeostatic eutrophic conditions as well as in the inimical environs of injury and/or disease. This biological system is highly regulated through reciprocal, complimentary, and often redundant upstream and downstream molecular and cellular elements and feedback controls. Key endogenous factors of the guanosine-dependent cyclic nucleotide cascade include upstream gaseous activating ligands (nitric oxide, carbon monoxide), downstream substrates (cGMP-gated ion channels, cGMP-dependent protein kinases), and cGMP hydrolyzing phosphodiesterases. This intricate system also has capacity to "cross-talk" with parallel adenosine-dependent cyclic nucleotide machinery. Numerous complexes of ligands, enzymes, cofactors, and substrates present significant targets for pharmacologic modulation at the cellular, genetic, and/or molecular level eventuating therapeutically as constructive functional responses observed in vascular physiology and/or pathophysiology. Interestingly, emerging evidence based largely on transgenic mouse models challenges the historically accepted concept that this signaling system functions principally as a therapeutic modality in cardiac and vascular tissues. The general purpose of this update is to provide current information on recently described neoteric agents that impact multifaceted and critical cGMP-dependent signaling in the vascular system. Emphasis will be placed on novel agents that exert significant and often multiple actions on upstream and downstream sites and are capable of eliciting robust effects on guanosine-dependent cellular actions. Individual sections will be devoted to agents that rely on an intact and functional cyclase heme and those that operate independently of the sGC heme. Attention will be placed on the physiologic and pathophysiologic clinical manifestations of these pharmacologic regimens. This review will conclude with some thoughts for future directions for study and continued discovery of novel sGC/cGMP controllers in the vascular system at the basic science and clinical levels.

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Inhibition of glucose transport by cyclic GMP in cardiomyocytes

Cited by 18 publications

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Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo

Regulation of cardiac long-chain fatty acid and glucose uptake by translocation of substrate transporters

Pharmacologic Modulators of Soluble Guanylate Cyclase/Cyclic Guanosine Monophosphate in the Vascular System - From Bench Top to Bedside

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