Impaired regulation of the TNF-α converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans

Monroy, Adriana; Kamath, Subhash; Chávez, Alberto O.; Centonze, Victoria E.; Veerasamy, Mangalakumar; Barrentine, Andrea; Wewer, J. J.; Coletta, Dawn K.; Jenkinson, Christopher P.; Jhingan, Ram; Smokler, D.; Reyna, Sara M.; Musi, Nicolas; Khokka, Rama; Federici, Massimo; Tripathy, Devjit; DeFronzo, Ralph A.; Folli, Franco

doi:10.1007/s00125-009-1451-3

Cited by 96 publications

(62 citation statements)

References 51 publications

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“…sortilin reduction to be mediated at least partially through the post-translational modification (shedding) involving TACE activity (25), which could be activated by a PKC activator, TPA (26). Intriguingly, several recent studies have demonstrated that TACE activity is increased in the skeletal muscles of obese type 2 diabetes patients and in lipid-induced insulin resistance (43,44). In addition, increased TACE activity has been directly implicated in the pathogenesis of insulin resistance, which is generally explained by the augmented secretion of TNF-␣ (43,45,46).…”

Section: Discussionmentioning

confidence: 99%

Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking in C2C12 Myotubes

Tsuchiya

Hatakeyama

Emoto

et al. 2010

Journal of Biological Chemistry

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Elevated saturated FFAs including palmitate (C16:0) are a primary trigger for peripheral insulin resistance characterized by impaired glucose uptake/disposal in skeletal muscle, resulting from impaired GLUT4 translocation in response to insulin. We herein demonstrate that palmitate induces down-regulation of sortilin, a sorting receptor implicated in the formation of insulin-responsive GLUT4 vesicles, via mechanisms involving PKC and TNF-␣-converting enzyme, but not p38, JNK, or mitochondrial reactive oxygen species generation, leading to impaired GLUT4 trafficking in C2C12 myotubes. Intriguingly, unsaturated FFAs such as palmitoleate (C16:1) and oleate (C18:1) had no such detrimental effects, appearing instead to effectively reverse palmitate-induced impairment of insulin-responsive GLUT4 recycling along with restoration of sortilin abundance by preventing aberrant PKC activation. On the other hand, shRNA-mediated reduction of sortilin in intact C2C12 myotubes inhibited insulin-induced GLUT4 recycling without dampening Akt phosphorylation. We found that the peroxisome proliferator-activated receptor ␥ agonist troglitazone prevented the palmitate-induced sortilin reduction and also ameliorated insulin-responsive GLUT4 recycling without altering the palmitate-evoked insults on signaling cascades; neither highly phosphorylated PKC states nor impaired insulin-responsive Akt phosphorylation was affected. Taken together, our data provide novel insights into the pathogenesis of PKC-dependent insulin resistance with respect to insulin-responsive GLUT4 translocation, which could occur not only through defects of insulin signaling but also via a reduction of sortilin, which directly controls trafficking/sorting of GLUT4 in skeletal muscle cells. In addition, our data suggest the insulin-sensitizing action of peroxisome proliferator-activated receptor ␥ agonists to be at least partially mediated through the restoration of proper GLUT4 trafficking/sorting events governed by sortilin.Skeletal muscle cells as well as adipocytes exhibit the highest levels of insulin-stimulated glucose uptake, which is achieved by translocation of the insulin-responsive glucose transporter (GLUT4) from intracellular storage compartment(s) to the plasma membrane (1). It has become increasingly apparent that sortilin, a type I transmembrane protein originally identified as a major component of GLUT4-containing vesicles from rat adipocytes (2, 3), plays crucial roles in the development of the insulin-responsive GLUT4 translocation system not only in adipocytes (4, 5) but also in skeletal muscle cells (6). Evidence available thus far indicates sortilin to be directly involved in the biogenesis of insulin-responsive GLUT4 storage vesicles by regulating sorting events of GLUT4 protein between the transGolgi network and endosomes (4, 5, 7), and experimental suppression of sortilin in adipocytes has been shown to inhibit insulin-responsive GLUT4 translocation (4).Intriguingly, a recent report demonstrated sortilin expression to be significantly reduce...

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Section: Discussionmentioning

confidence: 99%

Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking in C2C12 Myotubes

Tsuchiya

Hatakeyama

Emoto

et al. 2010

Journal of Biological Chemistry

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“…It has also been reported that Type 1 diabetes is associated cancer risk in a population-based study (Zendehdel et al, 2003). It is well accepted that infl ammation is closely associated with diabetes: TNF-α converting enzyme (TACE) activity as well as TNF-α is increased in diabetic patients (Fornoni et al, 2008;Monroy et al, 2009). Considering the fact that shedding of syndecan-1 is paralled by TNF-α release, it is possible that diabetes could be lead to cancer development via TACE and TNF-α system (Andrian et al, 2005).…”

Section: Diabetes and Cancermentioning

confidence: 99%

Syndecan as a Messenger to Link Diabetes and Cancer

Kim

Raman²

2011

Biomolecules and Therapeutics

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Cell surface syndecans are membrane-anchored proteoglycans. These glycoproteins have covalently linked glycosaminoglycan side chains. They interact via their extracellular part with various growth factors, extracellular matrix components, other cell surface molecules, and proteins involved in the regulation of blood coagulation. Thus the syndecans involve in synchronized expression patterns during embryogenesis and malignant transformation. These cell-cell interactions via their extracellular matrix ligands control cell proliferation, dynamic cytoskeletal remodeling, apoptosis and gene expression.Over the last few years, it has been widely accepted that heparan sulfate proteoglycans play a role in growth control, cell spreading, cellular recognition, cellular adhesion, and signaling, possibly as co -receptors with integrins, IGF-1R and cell -cell adhesion molecules, including fi bronectin, vitronectin, laminins, and the fi brillar collagens (Bernfi eld et al., 1999;Woods, 2001;Alexopoulou et al., 2007;Beauvais and Rapraeger, 2010). In addition, all syndecans have dibasic peptide sequence adjacent to the plasma membrane. Thus, the extracellular domains of syndecans could be cleaved by extracellular proteases. Syndecan's ectodomains have been shown to regulate a multitude of biological functions in celldependent and cell-independent approaches (Li et al., 2002;Endo et al., 2003;Elenius et al., 2004). Soluble syndecans also convert the membrane-bound receptors into soluble effectors/or antagonists. The soluble ectodomains of syndecans can compete with intact syndecans for extracellular ligands (Steinfeld et al., 1996). In this review, we will discuss the general Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed. Abstractfeatures and their conventional roles in signaling with co-receptors. Finally, we will explore the emerging roles of syndecans in the pathophysiology of human diseases, especially type 2 diabetes. SYNDECAN STRUCTUREAll the syndecans are a type 1 transmembrane proteins that are expressed in almost every cell of the body. Four members of syndecan family have been identifi ed in mammalians such as syndecan-1, 2, 3, and 4. Syndecan-1 analogs are also identifi ed in other mammals such as mouse, rat, dog, chimpanzee, guinea pig, Chinese hamster, cat and chicken. The extracellular domains of human and mouse syndecan-1 display approximately 70% sequence homology whereas the transmembrane domain and cytoplasmic domain show 96 % and 100% sequence homology, respectively. Synthesis of four syndecan core proteins are ...

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Section: Effects Of Adam17 Gene Polymorphisms On the Adam17 Expressionmentioning

confidence: 99%

“…In humans with metabolic disorders, such as obesity and type 2 diabetes, the co-occurrence of lipotoxicity and glucotoxicity has been found to increase the ADAM17 activity by decreasing the tissue inhibitor of metalloproteinase 3 (TIMP3) expression, while an increased ADAM17 activity has been reported to correlate with insulin resistance 31) . Therefore, ADAM17 Therefore, the rs1524668 ADAM17 polymorphism is likely to be one a key determinant of an increased occurrence of the PACI stroke subtype, while elevation of the ADAM17 mRNA expression confirms the role of ADAM17 in the pathophysiology of IS, with potentially important therapeutic implications.…”

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confidence: 99%

Association between ADAM17 Promoter Polymorphisms and Ischemic Stroke in a Chinese Population

Cui

et al. 2014

JAT

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Aim: Stroke is a leading cause of death and disability worldwide. Most ischemic strokes (IS) are caused by atherosclerosis. Recently, the pivotal role of ADAM17 in atherosclerosis has been thoroughly addressed. However, the association between ADAM17 and IS has not yet been thoroughly explored. The present study therefore aimed to investigate the association between disintegrin and metalloproteinase 17 (ADAM17) gene polymorphisms and the risk of ischemic stroke (IS). Methods: The associations between five ADAM17 promoter polymorphisms and the risk of IS were assessed in 342 patients with IS and 296 age-matched healthy individuals in a case-control study. Results: The allele and genotype frequencies of the ADAM17 polymorphisms (rs11684747, rs11689958, rs12692386, rs55790676 and rs1524668) did not differ significantly between the IS patients and healthy control group subjects. In addition, no significant associations were detected between the ADAM17 haplotypes and IS. The mean intima-media thickness in the IS patients was not associated with the ADAM17 polymorphisms. When the IS patients were stratified according to their OCSP classification, the genotype frequencies of the ADAM17-rs1524668 polymorphism exhibited a significant association with the PACI subtype of IS. Moreover, the ADAM17-rs12692386 A＞G polymorphism was found to be associated with a higher ADAM17 mRNA expression. Conclusions: The SNPs in the ADAM17 promoter region do not appear to be major contributors to the pathogenesis of IS. However, the rs12692386 G ADAM17 allele is correlated with a higher expression of ADAM17 mRNA, which may play a role in increasing inflammation in IS patients. Furthermore, the ADAM17-rs1524668 polymorphism is linked to a higher risk of PACI-type stroke, confirming the role of ADAM17 in the pathophysiology of PACI, with potentially important therapeutic implications. and the third most common cause of death in many developed and developing countries. Approximately 80% of stroke cases involve ischemic stroke (IS) 1) , which is primarily caused by atherosclerosis, a chronic inflammatory disease of the vessel wall 2) . ADAM (a disintegrin and metalloproteinase) genes, which are characterized by their metalloproteinase domain and disintegrin-cysteine rich region, are essential for a number of biological processes, including inflammation, cell proliferation and migration, immunity and You Li and Li-Li Cui contributed equally to this work. 879 ADAM17 Polymorphisms and Ischemic Stroke Materials and Methods SubjectsA total of 342 ischemic stroke patients (mean age, 70.30±10.75 years) were recruited from the First Affiliated Hospital of Guangdong Medical College between 2012 and 2013. An IS diagnosis was established based on the patient's clinical signs and symptoms. All patients underwent computed tomography (CT) scans and/or magnetic resonance imaging (MRI) as well as standardized blood tests. Based on the clinical manifestations and neuroimaging data, two neurologists classified the ischemic strokes into four subtypes using eithe...

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Impaired regulation of the TNF-α converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans

Cited by 96 publications

References 51 publications

Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking in C2C12 Myotubes

Palmitate-induced Down-regulation of Sortilin and Impaired GLUT4 Trafficking in C2C12 Myotubes

Syndecan as a Messenger to Link Diabetes and Cancer

Association between ADAM17 Promoter Polymorphisms and Ischemic Stroke in a Chinese Population

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