Globular adiponectin induces LKB1/AMPK-dependent glucose uptake via actin cytoskeleton remodeling

Vu, Vivian; Bui, Phuong; Eguchi, Megumi; Xu, Aimin; Sweeney, Gary

doi:10.1530/jme-13-0059

Cited by 28 publications

(17 citation statements)

References 46 publications

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“…Recent studies have also shown that the LKB1/AMPK pathway is implicated in adiponectin-induced various biologic responses. For example, adiponectin-induced glucose uptake and suppression of breast cancer cells migration are mediated via LKB1/AMPK-dependent manner (Vu et al, 2013). Although it is well known that LKB1 is implicated in adiponectin-induced biologic responses, the role of LKB1 signaling in antioxidative effect induced by adiponectin has not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…For example, LKB1 deficiency leads to inactivation of AMPK, and LKB1-induced tumor suppression and modulation of cellular energy homeostasis are mediated through activation of AMPK (Shaw et al, 2004;Alessi et al, 2006). Furthermore, LKB1/AMPK axis is used for adiponectininduced various biologic responses (Miller et al, 2011;Vu et al, 2013). However, the effect of adiponectin on LKB1 signaling and its role in the modulation of ROS production in macrophages have not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

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Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathway

2014

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Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. Although excessive reactive oxygen species (ROS) production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits, including Nox2 and p22 phox , via modulation of nuclear factor-kB pathway. Furthermore, pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanolinduced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathway

2014

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“…Adiponectin directly regulates glucose metabolism and insulin sensitivity. Adiponectin, via activation of AMPK and adiponectin, stimulates GLUT4 translocation and glucose uptake [124]. Adiponectin receptors activate AMPK, PPAR- α , and p38 MAPK to increase insulin sensitivity [58, 125].…”

Section: Adiponectin Aging and Diabetesmentioning

confidence: 99%

Association between Risk Factors for Vascular Dementia and Adiponectin

Song

Lee

Park

et al. 2014

BioMed Research International

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Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

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“…Glucose uptake assays were performed in C2C12 and L6 myotubes using 2-deoxy- [ 3 H]-glucose as tracer as described in our previous study (20). For ex vivo glucose uptake assay, mice fasted for 4 h were anesthetized.…”

Section: Analysis Of Glucose Uptake and Glut4 Translocation In Musclementioning

confidence: 99%

“…Isolated extensor digitorum longus (EDL) or soleus muscles were stimulated without or with insulin 60 mU/mL followed by measurement of 2-deoxy-[ 3 H]-glucose uptake (21). For determination of GLUT4 translocation, an antibodycoupled densitometric assay was used to measure the content of surface Myc-GLUT4 in L6 myotubes stably expressing Myc-tagged GLUT4 as described in previous studies (20,22).…”

Section: Analysis Of Glucose Uptake and Glut4 Translocation In Musclementioning

confidence: 99%

The Adaptor Protein APPL2 Inhibits Insulin-Stimulated Glucose Uptake by Interacting With TBC1D1 in Skeletal Muscle

et al. 2014

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Insulin stimulates glucose uptake by promoting the trafficking of GLUT4 to the plasma membrane in muscle cells, and impairment of this insulin action contributes to hyperglycemia in type 2 diabetes. The adaptor protein APPL1 potentiates insulin-stimulated Akt activation and downstream actions. However, the physiological functions of APPL2, a close homolog of APPL1, in regulating glucose metabolism remain elusive. We show that insulin-evoked plasma membrane recruitment of GLUT4 and glucose uptake are impaired by APPL2 overexpression but enhanced by APPL2 knockdown. Likewise, conditional deletion of APPL2 in skeletal muscles enhances insulin sensitivity, leading to an improvement in glucose tolerance. We identified the Rab-GTPaseactivating protein TBC1D1 as an interacting partner of APPL2. Insulin stimulates TBC1D1 phosphorylation on serine 235, leading to enhanced interaction with the BAR domain of APPL2, which in turn suppresses insulinevoked TBC1D1 phosphorylation on threonine 596 in cultured myotubes and skeletal muscle. Substitution of serine 235 with alanine diminishes APPL2-mediated inhibition on insulin-dependent TBC1D1 phosphorylation on threonine 596 and the suppressive effects of TBC1D1 on insulin-induced glucose uptake and GLUT4 translocation to the plasma membrane in cultured myotubes. Therefore, the APPL2-TBC1D1 interaction is a key step to fine tune insulin-stimulated glucose uptake by regulating the membrane recruitment of GLUT4 in skeletal muscle.

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Globular adiponectin induces LKB1/AMPK-dependent glucose uptake via actin cytoskeleton remodeling

Cited by 28 publications

References 46 publications

Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathway

Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathway

Association between Risk Factors for Vascular Dementia and Adiponectin

The Adaptor Protein APPL2 Inhibits Insulin-Stimulated Glucose Uptake by Interacting With TBC1D1 in Skeletal Muscle

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