Akt2 regulates Rac1 activity in the insulin-dependent signaling pathway leading to GLUT4 translocation to the plasma membrane in skeletal muscle cells

Nozaki, Shinsuke; Takeda, Tomoya; Kitaura, Takuya; Takenaka, Nobuyuki; Kataoka, Tohru; Satoh, Takaya

doi:10.1016/j.cellsig.2013.02.023

Cited by 37 publications

(50 citation statements)

References 32 publications

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“…In addition, it has been shown that a constitutively activated mutant of PI3K induces Rac1 activation [59,60,61]. Therefore, it is feasible that Rac1 is regulated downstream of PI3K in insulin signaling.…”

Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

“…In another proposed model, Akt2 and Rac1 function in tandem, constituting a signaling cascade together with intermediary elements [59,60,61] (Figure 2B). Rac1 activation by insulin stimulation or ectopic expression of constitutively activated PI3K was blocked by knockdown of Akt2 [59,60].…”

Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

“…Rac1 activation by insulin stimulation or ectopic expression of constitutively activated PI3K was blocked by knockdown of Akt2 [59,60]. Furthermore, GLUT4 translocation induced by constitutively activated Akt2 was totally down-regulated when Rac1 was knocked down in cultured myoblasts and mouse gastrocnemius muscle [60].…”

Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

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Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Satoh

2014

IJMS

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101

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Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted.

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Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

Section: Mechanisms For Rac1 Activation In Response To Insulin Stimentioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Satoh

2014

IJMS

Self Cite

101

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“…Recent studies suggest that ROS derived from Nox play regulatory "second-messenger" roles in GSIS [30,34]. Indeed, previous studies showed that Rac1 plays a pivotal role in insulin-stimulated glucose uptake in skeletal muscle, which is mediated by GLUT4 translocation to the plasma membrane [35]. In addition to the positive modulatory roles for ROS in GSIS, recent evidence also implicates negative modulatory roles for ROS in the induction of oxidative stress and metabolic dysregulation of islet β cells under the duress of glucolipotoxicity, cytokines, and ceramide [8].…”

Section: The Impairment Of β Cell Function Induced By Oxidative Stresmentioning

confidence: 99%

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Zhou

Yu²,

Shen³

et al. 2015

Cell Physiol Biochem

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Background: The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity. Methods: In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed. Results: ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells. Conclusions: Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production.

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“…IGF2 and AKT2 can take part in the insulin signaling pathway and promote energy utilization (Nozaki et al, 2013;Bach, 2015). The increasing expression of AKT2 could modulate the insulin signaling pathway and induce the translocation of insulin-sensitive GLUT4 from intracellular pools to the plasma membrane, thereby stimulating the absorption of more glucose from blood to balance the glucose efflux activity caused by gSWEET1 (Stuart et al, 2009;Leto and Saltiel, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cloning and functional analysis of goat SWEET1

Zhu

Bao

et al. 2015

Genet. Mol. Res.

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ABSTRACT. SWEETs are a recently discovered class of sugar transporters that mediate glucose uptake in the intestine and mammary glands. Our objectives were to clone goat SWEET1 and conduct a functional analysis of its effect on glucose efflux in goat mammary gland epithelial cells. We cloned and sequenced the goat SWEET1 gene from goat mammary glands, then conducted an analysis of the structure of goat SWEET1, including a prediction of the transmembrane helices and potential N-glycosylation sites. To investigate the biological function of goat SWEET1, we also generated goat SWEET1-transfected goat mammary gland epithelial cells using the eukaryotic expression vector pcDNA3.1-gSWEET1. Goat SWEET1 overexpression can reduce glucose absorption in mammary gland epithelial cells with increasing expression of GLUT1, GLUT4, and GLUT12, which may be attributed to glucose efflux arising from the leading role played by goat SWEET1. This study will improve our understanding of the glucose balance in mammary glands and the level of glucose in milk.

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Akt2 regulates Rac1 activity in the insulin-dependent signaling pathway leading to GLUT4 translocation to the plasma membrane in skeletal muscle cells

Cited by 37 publications

References 32 publications

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Cloning and functional analysis of goat SWEET1

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