Cardiac insulin resistance is associated with an impaired recruitment of phosphatidylinositol 3-kinase to GLUT4 vesicles

Eckel, Jürgen; Till, Martin; Uphues, Ingo

doi:10.1038/sj.ijo.0801295

Cited by 5 publications

(3 citation statements)

References 5 publications

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“…We chose to study the myocardial glucose transporters and the related adaptations of insulin signal transduction proteins during an IUGR gestation in fetal sheep to help understand how the fetal myocar~ium ada?ts to glucose deficiency and lactate excess. Such information will provide a basis for understanding how such in utero adaptations might change over the animal's life span and lead to later life metabolic complications, such as adult myocardial insulin resistance (7,8). To date, there has been no study that defines those mechanisms in glucose transport or insulin signaling that might develop in the myocardium of the (UGR fetus to account for such adaptations.…”

Section: Introductionmentioning

confidence: 99%

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Barry

Davidsen

Limesand

et al. 2006

Exp Biol Med (Maywood)

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Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut-4 PM and IRbeta protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.

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Section: Introductionmentioning

confidence: 99%

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Barry

Davidsen

Limesand

et al. 2006

Exp Biol Med (Maywood)

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“…[15][16][17][18] Thus, factors involved in the rearrangement of the cytoskeleton may contribute to the regulation of glucose transport and may additionally modify the insulin sensitivity of this process. In the light of these considerations, we have now used adult cardiomyocytes [19][20][21][22] in order to assess the potential contribution of the LO pathway in the rearrangement of actin cytoskeletal elements and the functional implications for GLUT4 trafficking in these cells.…”

Section: Introductionmentioning

confidence: 99%

Eicosanoids and the Regulation of Cardiac Glucose Transport

Dransfeld

Rakatzi

Sasson

et al. 2002

Annals of the New York Academy of Sciences

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Intact actin microfilaments are necessary for insulin‐regulated GLUT4 translocation from intracellular pools to the plasma membrane. Products of the lipoxygenase (LO) pathway were shown to be implicated in the regulation of actin cytoskeleton rearrangement. The aim of this study was to examine the role of these LO products for cardiac insulin signaling and glucose uptake, GLUT4 translocation, and actin‐based cytoskeleton structure. Exposure of cardiomyocytes to esculetin or NDGA, two structurally different LO inhibitors, induced a complete inhibition of insulin‐stimulated glucose uptake, whereas control cells showed a threefold stimulation by insulin. Addition of 12(S)‐HETE rendered the NDGA‐treated cells insulin‐sensitive. Early insulin signaling was not changed in cells exposed to LO inhibitors. Cell surface biotinylation of control cells showed a twofold increase of GLUT4 at the cell surface after insulin stimulation. In contrast, the LO inhibitors induced a complete inhibition of insulin‐stimulated GLUT4 translocation. Labeling of the F‐actin cytoskeleton revealed a prominent disassembly of actin fibers in cells exposed to the LO inhibitors. In conclusion, we show here that products of the LO reaction participate in the organization of the actin network in ventricular cardiomyocytes. Inhibition of LO blocks GLUT4 translocation without affecting insulin signaling events. These data suggest that products of the LO reaction participate in the regulation of glucose transport by contribution to a rearrangement of actin cytoskeletal elements.

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“…The potential involvement of this eicosanoid in the organization of the actin network in the cardiomyocyte has not been investigated to date, although 12(S)-HETE has been shown to play an important role in the cardioprotective effect of ischaemic preconditioning [18][19][20]. In the present study we have used our well characterized adult cardiomyocyte system [21][22][23][24] to (1) assess the possible contribution of the 12-LO pathway in the rearrangement of actin cytoskeletal elements and (2) determine its potential implications for insulin-regulated trafficking of GLUT4. The results suggest that the 12-LO pathway participates in the organization of the actin cytoskeletal network, and thus, may operate as an important determinant in the insulin-sensitive cardiac glucose uptake system.…”

Section: Introductionmentioning

confidence: 99%

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements

Dransfeld

Rakatzi

Sasson

et al. 2001

Biochemical Journal

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Intact actin microfilaments are required for insulin-regulated glucose transporter isoform 4 (GLUT4) translocation to the plasma membrane. Lipoxygenase (LO) metabolites have recently been shown to contribute to the regulation of actin cytoskeleton rearrangement. In the present investigation, ventricular cardiomyocytes were used to study the effects of two structurally different LO inhibitors (esculetin and nordihydroguaiaretic acid) on insulin signalling events, glucose uptake, GLUT4 translocation and the actin network organization. Insulin stimulation increased glucose uptake 3-fold in control cells, whereas LO inhibition completely blocked this effect. This was paralleled by a slight reduction in the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2. However, inhibition of 12-LO did not affect the association of phosphatidylinositol 3-kinase with IRS-1 and the phosphorylation of Akt\protein kinase B in response to insulin. Addition of 12(S)-

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Cardiac insulin resistance is associated with an impaired recruitment of phosphatidylinositol 3-kinase to GLUT4 vesicles

Cited by 5 publications

References 5 publications

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction

Eicosanoids and the Regulation of Cardiac Glucose Transport

Eicosanoids participate in the regulation of cardiac glucose transport by contribution to a rearrangement of actin cytoskeletal elements

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