Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation

Shimoyama, Tatsuhiro; Yamaguchi, Shinya; Takahashi, Kazuto; Katsuta, Hidenori; Ito, Eisuke; Seki, Hiroyuki; Ushikawa, Kenji; Katahira, Hiroshi; Yoshimoto, Katsuhiko; Ohno, Hideki; Nagamatsu, Shinya; Ishida, Hideyuki

doi:10.1016/j.metabol.2006.01.019

Cited by 22 publications

(12 citation statements)

References 41 publications

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“…Alternatively, the effect of H 2 O 2 on this process may depend on the time of exposure. Similar differences in H 2 O 2 action have been observed for insulin, wherein acutely low H 2 O 2 concentrations can mimic hormone action, while, chronically, they induce insulin resistance through alteration of insulin-mediated activation of the insulin signaling pathway and abnormal localization of insulin signaling molecules, such as PI3K (36,40,44).…”

Section: Discussionsupporting

confidence: 53%

Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes

Pelletier¹,

Coderre²

2007

American Journal of Physiology-Endocrinology and Metabolism

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Pelletier A, Coderre L. Ketone bodies alter dinitrophenolinduced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes. Am J Physiol Endocrinol Metab 292: E1325-E1332, 2007. First published January 16, 2007; doi:10.1152/ajpendo.00186.2006.-In aerobic conditions, the heart preferentially oxidizes fatty acids. However, during metabolic stress, glucose becomes the major energy source, and enhanced glucose uptake has a protective effect on heart function and cardiomyocyte survival. Thus abnormal regulation of glucose uptake may contribute to the development of cardiac disease in diabetics. Ketone bodies are often elevated in poorly controlled diabetics and are associated with increased cellular oxidative stress. Thus we sought to determine the effect of the ketone body ␤-hydroxybutyrate (OHB) on cardiac glucose uptake during metabolic stress. We used 2,4-dinitrophenol (DNP), an uncoupler of the mitochondrial oxidative chain, to mimic hypoxia in cardiomyocytes. Our data demonstrated that chronic exposure to OHB provoked a concentration-dependent decrease of DNP action, resulting in 56% inhibition of DNP-mediated glucose uptake at 5 mM OHB. This was paralleled by a diminution of DNP-mediated AMP-activated protein kinase (AMPK) and p38 MAPK phosphorylation. Chronic exposure to OHB also increased reactive oxygen species (ROS) production by 1.9-fold compared with control cells. To further understand the role of ROS in OHB action, cardiomyocytes were incubated with H 2O2. Our results demonstrated that this treatment diminished DNP-induced glucose uptake without altering activation of the AMPK/p38 MAPK signaling pathway. Incubation with the antioxidant N-acetylcysteine partially restored DNP-mediated glucose but not AMPK/p38 MAPK activation. In conclusion, these results suggest that ketone bodies, through inhibition of the AMPK/p38 MAPK signaling pathway and ROS overproduction, regulate DNP action and thus cardiac glucose uptake. Altered glucose uptake in hyperketonemic states during metabolic stress may contribute to diabetic cardiomyopathy. glucose transport; hypoxia; 2,4-dinitrophenol; adenosine monophosphate-activated protein kinase CARDIOVASCULAR DISEASE is a well-known complication of diabetes. Diabetes increases the risk of mortality from heart disease by 4.0-to 6.6-fold and 6.2-to 17.1-fold in men and women, respectively (26). It also significantly worsens the prognosis after heart failure, despite the fact that infarct size is often smaller in diabetics (47). Poorly controlled type 1 diabetic patients often have elevated concentrations of ketone bodies that can reach levels as high as 10 mM during severe ketosis (27). Increased ketone body levels have also been observed in type 2 diabetes (3) and in congestive heart failure (31). Furthermore, in the latter condition, increased plasma ketone body concentrations correlate with the severity of cardiac dysfunction (31).More than 64% of type 1 and 34% of type 2 diabetic patients have inadequate cardiac glucose uptake (34, 51), ...

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Section: Discussionsupporting

confidence: 53%

Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes

Pelletier¹,

Coderre²

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…ated with the induction of intracellular oxidative stress by the modified lipoproteins. It has been reported that the oxidative stress induced by hydrogen peroxide impairs insulin-stimulated GLUT4 translocation through the impairment of the cellular response to insulin (99,100). However, we can exclude the implication of oxidative stress in oxLDL-treated 3T3-L1.…”

Section: Oxldl Impair Insulin Signaling In Adipocytes 839mentioning

confidence: 58%

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

Scazzocchio

Varı̀

D’Archivio

et al. 2009

Journal of Lipid Research

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Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (240%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (270%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser 307 phosphorylation. This process was largely mediated by the activation of the inhibitor of kB-kinase b (IKKb) and the c-Jun NH 2 -terminal kinase ( JNK). Moreover, the activation of IKKb positively regulated the nuclear content of nuclear factor kB (NF-kB), by inactivating the inhibitor of NF-kB (IkBa). The activated NF-kB further impaired per se GLUT4 functionality. Specific inhibitors of IKKb, JNK, and NF-kB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance.-Scazzocchio, B., R. Varì, M. DʼArchivio, C. Santangelo, C. Filesi, C. Giovannini, and R. Masella. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases. J. Lipid Res. 2009. 50: 832-845.

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“…Cells were seeded and fed every 2 days in DMEM containing 25 mmol/l glucose supplemented with 50 U/ml penicillin, 50 g/ml streptomycin, 100 mmol/l MEM sodium pyruvate, and 10% FCS. Cells were grown under 5% CO 2 at 37°C (36,49). At confluence, differentiation was induced by addition of medium containing 500 mol/l isobutylmethylxanthine (Sigma), 250 nmol/l dexamethasone (Sigma), and 1.7 mol/l insulin.…”

Section: Methodsmentioning

confidence: 99%

JNK- and IκB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro

Takahashi¹,

Yamaguchi²,

Shimoyama³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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H. JNK-and IB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro. Am J Physiol Endocrinol Metab 294: E898-E909, 2008. First published February 26, 2008 doi:10.1152/ajpendo.00131.2007.-Obese conditions increase the expression of adipocytokine monocyte chemoattractant protein-1 (MCP-1) in adipose tissue as well as MCP-1 plasma levels. To investigate the mechanism behind increased MCP-1, we used a model in which 3T3-L1 adipocytes were artificially hypertrophied by preloading with palmitate in vitro. As observed in obesity, under our model conditions, palmitate-preloaded cells showed significantly increased oxidative stress and increased MCP-1 expression relative to control cells. This increased MCP-1 expression was enhanced by adding exogenous tumor necrosis factor-␣ (TNF-␣; 17.8-fold vs. control cells, P Ͻ 0.01) rather than interleukin-1␤ (IL-1␤; 2.6-fold vs. control cells, P Ͻ 0.01). However, endogenous TNF-␣ and IL-1␤ release was not affected in hypertrophied cells, suggesting that these endogenous cytokines do not mediate hypertrophy-induced increase in MCP-1. MCP-1 secretion from hypertrophied cells was significantly decreased by treatment with antioxidant N-acetyl-cysteine, JNK inhibitors SP600125 and JIP-1 peptide, and IB phosphorylation inhibitors BAY 11-7085 and BMS-345541 (P Ͻ 0.01). MCP-1 secretion was not affected by peroxisome proliferator-activated receptor-␥ (PPAR␥) antagonists assayed. Adiponectin, another adipocytokine studied in parallel, also showed increased release in hypertrophy relative to control cells. But in contrast to MCP-1, adiponectin release was significantly suppressed by both exogenous TNF-␣ and IL-1␤ as well as by PPAR␥ antagonists bisphenol A diglycidyl ether and T0070907 (P Ͻ 0.01). JNK inhibitors and IB phosphorylation inhibitors showed no significant effect on adiponectin. We conclude that adipocyte hypertrophy through palmitate loading causes oxidative stress, which in turn increases MCP-1 expression and secretion through JNK and IB signaling. In contrast, the parallel increase in adiponectin expression appears to be related to the PPAR␥ ligand properties of palmitate.c-Jun NH 2-terminal kinase; monocyte chemoattractant protein-1; tumor necrosis factor-␣; interleukin-1␤ ADIPOCYTES STOCKPILE TRIGLYCERIDES, and increasing adipocyte size or hypertrophy accompanies the increased intracellular triglyceride content (43). In addition to triglyceride stockpiling, adipocytes function in endocrine signaling by secreting adipocytokines such as adiponectin, tumor necrosis factor-␣ (TNF-␣), interleukin-1␤ (IL-1␤), and monocyte chemoattractant protein-1 (MCP-1) (31). Adipocytokine MCP-1 is a potent chemotactic factor for monocytes and is predominantly produced by macrophages and vascular endothelial cells (34). MCP-1 expression in adipose tissue leads to macrophage infiltration into this tissue and insulin resistance under obese conditions (5,17,18). In vivo in obese mice, MCP-1 is abundantly exp...

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Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation

Cited by 22 publications

References 41 publications

Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes

Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

JNK- and IκB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro

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