Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway

Higaki, Yasuki; Mikami, Toshio; Fujii, Nobuharu; Hirshman, Michael F.; Koyama, Katsuhiro; Seino, Tetsuya; Tanaka, Keitaro; Goodyear, Laurie J.

doi:10.1152/ajpendo.00150.2007

Cited by 115 publications

(89 citation statements)

References 55 publications

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“…A potential downstream target of Sirt2 is Akt, which is involved in insulin signaling and promotes a glycolytic phenotype in various cell types (Elstrom et al, 2004;Higaki et al, 2008;Ramakrishnan et al, 2014). Acetylation of Akt at residue Lys20 prevents plasma membrane localization and activation of Akt by phosphatidylinositol 3-kinase (PI3K) (Sundaresan et al, 2011), whereas deacetylation of Akt by Sirt2 is reported to promote its activity Dan et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Acute stimulation of glucose influx by mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR/RAPTOR

Liemburg-Apers

Wagenaars

Smeitink

et al. 2016

Journal of Cell Science

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Mitochondria play a central role in cellular energy production, and their dysfunction can trigger a compensatory increase in glycolytic flux to sustain cellular ATP levels. Here, we studied the mechanism of this homeostatic phenomenon in C2C12 myoblasts. Acute (30 min) mitoenergetic dysfunction induced by the mitochondrial inhibitors piericidin A and antimycin A stimulated Glut1-mediated glucose uptake without altering Glut1 (also known as SLC2A1) mRNA or plasma membrane levels. The serine/threonine liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK) played a central role in this stimulation. In contrast, ataxiatelangiectasia mutated (ATM; a potential AMPK kinase) and hydroethidium (HEt)-oxidizing reactive oxygen species (ROS; increased in piericidin-A-and antimycin-A-treated cells) appeared not to be involved in the stimulation of glucose uptake. Treatment with mitochondrial inhibitors increased NAD + and NADH levels (associated with a lower NAD + :NADH ratio) but did not affect the level of Glut1 acetylation. Stimulation of glucose uptake was greatly reduced by chemical inhibition of Sirt2 or mTOR-RAPTOR. We propose that mitochondrial dysfunction triggers LKB1-mediated AMPK activation, which stimulates Sirt2 phosphorylation, leading to activation of mTOR-RAPTOR and Glut1-mediated glucose uptake.

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Section: Discussionmentioning

confidence: 99%

Acute stimulation of glucose influx by mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR/RAPTOR

Liemburg-Apers

Wagenaars

Smeitink

et al. 2016

Journal of Cell Science

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“…In particular, H2O2 uses the same pathway of insulin and causes downstream propagation of the signal producing typical metabolic actions of insulin. H2O2 induces an increase in glucose uptake by adipocytes and muscles [66], and also stimulates GLUT4 translocation and lipid synthesis in adipocytes [67].…”

Section: Oxidative Stress and Insulin Resistancementioning

confidence: 99%

Metabolic Syndrome, Aging and Involvement of Oxidative Stress

Bonomini¹,

Rodella²,

Rezzani³

2015

Aging and disease

467

308

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ABSTRACT:The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity-are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases. One of the defects in metabolic syndrome and its associated diseases is excess of reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. In this article we review current understandings of oxidative stress in metabolic syndrome related disease and its possible contribution to accelerated senescence.

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“…Propagation of the signal downstream yielded typical metabolic actions of insulin. In adipocytes and muscle, H 2 O 2 increased glucose uptake (174,238,431), and in adipocytes also stimulated GLUT4 translocation (273) and lipid synthesis (280).…”

Section: A Oxidants Have Insulin-mimicking Effectsmentioning

confidence: 99%

Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species

Bashan¹,

Kovsan²,

Kachko³

et al. 2009

Physiological Reviews

468

367

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Regulated production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) adequately balanced by antioxidant systems is a prerequisite for the participation of these active substances in physiological processes, including insulin action. Yet, increasing evidence implicates ROS and RNS as negative regulators of insulin signaling, rendering them putative mediators in the development of insulin resistance, a common endocrine abnormality that accompanies obesity and is a risk factor of type 2 diabetes. This review deals with this dual, seemingly contradictory, function of ROS and RNS in regulating insulin action: the major processes for ROS and RNS generation and detoxification are presented, and a critical review of the evidence that they participate in the positive and negative regulation of insulin action is provided. The cellular and molecular mechanisms by which ROS and RNS are thought to participate in normal insulin action and in the induction of insulin resistance are then described. Finally, we explore the potential usefulness and the challenges in modulating the oxidant-antioxidant balance as a potentially promising, but currently disappointing, means of improving insulin action in insulin resistance-associated conditions, leading causes of human morbidity and mortality of our era.

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Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway

Cited by 115 publications

References 55 publications

Acute stimulation of glucose influx by mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR/RAPTOR

Acute stimulation of glucose influx by mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR/RAPTOR

Metabolic Syndrome, Aging and Involvement of Oxidative Stress

Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species

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