Adenovirus infection results in alterations of insulin signaling and glucose homeostasis

Jiang, Shaoning; Gavrikova, T. A.; Pereboev, Alexander; Messina, Joseph L.

doi:10.1152/ajpendo.00723.2009

Cited by 15 publications

(12 citation statements)

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“…2D and E). Recently, it has been reported that Ad-bgal injection in rat impaired glucose homeostasis at 4-6 days post-injection [16]. At both 7 and 14 days after Adbgal injection, no difference was noticed in glucose tolerance between saline-injected (control) and Ad-bgal-injected mice (data not shown).…”

Section: Liver Adenovirus-mediated Cpt1mt Expression Decreases Glucosmentioning

confidence: 78%

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

Monsenego¹,

Mansouri²,

Akkaoui³

et al. 2012

Journal of Hepatology

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Section: Liver Adenovirus-mediated Cpt1mt Expression Decreases Glucosmentioning

confidence: 78%

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

Monsenego¹,

Mansouri²,

Akkaoui³

et al. 2012

Journal of Hepatology

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“…10,11 Like other human adenoviruses, Ad36 downregulates IR, IRS1 or IRS2 activation, yet, Ad36 recruits the distal insulin signaling pathway (PI3K/AKT) via Ras activation, leading to greater Glut4 abundance and translocation and glucose disposal. 9– 11,13 …”

Section: Introductionmentioning

confidence: 99%

Insulin receptor-independent upregulation of cellular glucose uptake

et al. 2012

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Background Cellular glucose uptake can be enhanced by upregulating Ras signaling in either insulin-dependent or - independent manner. In presence of insulin and intact insulin signaling, Ras has a negligible role in glucose uptake. Conversely, when insulin signaling is impaired in obesity or diabetes, the insulin-independent Ras pathway may be valuable for enhancing glucose disposal. We previously reported that Ad36, a human adenovirus, enhances cellular glucose uptake by upregulating the Ras/Glut4 pathway. Here, we investigated if Ad36-upregulated Ras via the insulin-independent pathway, to enhance glucose uptake. Furthermore, uncontrolled upregulation of Ras is linked with oncogenic cell transformation, if the tumor-suppressor gene p53 is also downregulated. Hence, we determined if upregulation of Ras by Ad36 would induce oncogenic cell transformation. Finally, we determined the relevance of Ad36 to insulin resistance in humans. Methods Insulin receptor (IR) was knocked down with small interfering RNA in 3T3-L1 adipocytes, to determine if Ad36 increases the Ras/Glut4 pathway and glucose uptake without IR-signaling. Next, the effects of Ad36 on cell transformation and p53 abundance were determined. Finally, overweight or obese women were screened for seropositivity to Ad36, as an indicator of natural Ad36 infection. Associations of Ad36 infection with adiposity and C-reactive proteins (CRPs)—two key markers of insulin resistance, and with glucose disposal, were determined. Results Unaffected by IR knock-down, Ad36 significantly increased the Ras pathway, Glut4 translocation and glucose uptake in 3T3-L1 adipocytes. Despite Ras upregulation, Ad36 did not transform 3T3-L1 cells. This may be because Ad36 significantly increased p53 protein in 3T3-L1 cells or mice adipose tissue. Ad36 seropositivity was associated with greater adiposity and CRP levels, yet a significantly higher systemic glucose disposal rate. Conclusions Overall, the study offers Ras/Glut4 pathway as an alternate to enhance glucose disposal when insulin signaling is impaired, and, importantly, provides Ad36 as a tool to understand the modulation of that pathway.

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“…Liver tissues from each animal were homogenized in lysis buffer, as described previously (11,13,16,22). The tissue lysates were centrifuged, and the supernatants were stored at Ϫ80°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…The recombinant adenovirus vector expressing a dominant negative mutant (T183A/Y185F) of JNK1 (Ad-DN-JNK1) was purchased from Cell Biolabs (San Diego; ADV-115) and was rendered kinase dead by two mutations within the JNK kinase domain. The Ad vectors were amplified in 293A cells and purified twice by cesium chloride gradient ultracentrifugation followed by dialysis (11,13). The biological titer [plaque forming units (pfu)/ml] was determined by the TCID50 (tissue culture infectious dose 50) method (Adenovector Vector System) based on the development of a cytopathic effect in 293 cells.…”

Section: Methodsmentioning

confidence: 99%

“…The biological titer [plaque forming units (pfu)/ml] was determined by the TCID50 (tissue culture infectious dose 50) method (Adenovector Vector System) based on the development of a cytopathic effect in 293 cells. Replication-competent adenovirus contamination was not detected in purified virus stocks as screened by PCR with the primers flanking the E1 region (11,13). Rats were injected with the purified Ad vectors (10 10 pfu/rat) via the tail vein.…”

Section: Methodsmentioning

confidence: 99%

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Regulation of hepatic insulin receptor activity following injury

Jiang

Gavrikova

Messina

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Jiang S, Gavrikova TA, Messina JL. Regulation of hepatic insulin receptor activity following injury. Am J Physiol Gastrointest Liver Physiol 306: G886 -G892, 2014. First published April 3, 2014 doi:10.1152/ajpgi.00128.2013.-Impaired insulin receptor (IR) activity has been found in various models of insulin resistance, including models of injury or critical illness and Type 2 diabetes. However, mechanisms that modulate IR function remain unclear. With an animal model of critical-illness diabetes, we found insulin-induced IR tyrosine phosphorylation in the liver was impaired as early as 15 min following trauma and hemorrhage. Possible mechanisms for this defect were examined, including IR protein levels and IR posttranslational modifications. The total amounts of hepatic IR␣ and IR␤ subunits and the membrane localization of the IR were not altered by trauma and hemorrhage, and, likewise, no change in IR tyrosine nitration was found in the liver. However, there was a decrease in the level of protein O-linked ␤-N-acetlyglucosamine (O-GlcNac) modification on Ser/Thr in the liver following trauma and hemorrhage. Inhibition of JNK increased IR O-GlcNac modification, implicating an involvement of JNK. These findings suggest that a balance between O-GlcNac modification and JNK-induced phosphorylation may exist, with decreased Ser/Thr O-GlcNac modification following trauma and hemorrhage, allowing JNK to phosphorylate the IR on neighboring Ser/Thr residues, which subsequently inhibits IR activity. The present studies suggest potential mechanisms of hemorrhage-induced defects in IR activity and a potential role for acutely decreased O-GlcNac and increased serine phosphorylation of the IR.O-linked ␤-N-acetlyglucosamine; c-Jun NH2-terminal kinase; insulin resistance; liver; injury THE INSULIN RECEPTOR (IR) consists of two extracellular ␣ subunits and two transmembrane ␤ subunits, disulfide linked into an ␣ 2 ␤ 2 heterotetrameric complex. Binding of insulin to the ␣ subunit results in a conformational change and subsequent activation of the receptor's protein tyrosine kinase activity, which, in turn, activates downstream insulin signaling (14, 23). Defects in IR activity have been found in patients with Type 2 diabetes (23) and in various animal models of insulin resistance, including after sepsis (17) and viral infections (11). With animal models of surgical trauma and hemorrhage, we previously observed impaired IR activity following trauma and hemorrhage, which is characterized by defects in insulininduced IR phosphorylation on multiple tyrosine residues (12,13,15,16,21,22,25,26). Although the evidence suggests that acute and chronic regulation of IR contributes to impaired insulin sensitivity and glucose homeostasis, the molecular mechanisms underlying the impaired IR activation after injuries remain largely unclear.Possible mechanisms accounting for impaired insulin signaling at the level of IR include cell surface IR content or modification of IR enzymatic activity. Reduced IR cell surface content and insulin binding ca...

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Adenovirus infection results in alterations of insulin signaling and glucose homeostasis

Abstract: Jiang S, Gavrikova TA, Pereboev A, Messina JL. Adenovirus infection results in alterations of insulin signaling and glucose homeostasis.

Cited by 15 publications

References 50 publications

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

Insulin receptor-independent upregulation of cellular glucose uptake

Regulation of hepatic insulin receptor activity following injury

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