TITLE

Overexpression of Suppressor of Cytokine Signaling 3 in Adipose Tissue Causes Local but Not Systemic Insulin Resistance

AUTHOR(S)
Shi, Hang; Cave, Belinda; Inouye, Karen; Bjørbæk, Christian; Flier, Jeffrey S.
PUB. DATE
March 2006
SOURCE
Diabetes;Mar2006, Vol. 55 Issue 3, p699
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake. Moreover, SOCS3 is required for tumor necrosis factor-α full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake. Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear. We therefore generated a transgenic mouse (aP2-SOCS3 mouse) overexpressing SOCS3 in adipose tissue. Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes. This impaired insulin signaling in adipose tissue of aP2-SOCS3 mice causes decreased lipogenesis and blocks insulin's antilipolytic action. However, because of decreased energy partitioning in adipose tissue, aP2-SOCS3 mice are resistant to diet-induced obesity and are protected against systemic insulin resistance caused by a high-fat diet. Therefore, overexpression of SOCS3 in adipocytes causes local adipocyte insulin resistance, but it is not sufficient to cause systemic insulin resistance.
ACCESSION #
20209987

 

Related Articles

  • Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet M. Björnholm et al.: Insulin signalling in human adipocytes. Björnholm, M.; Al-Khalili, L.; Dicker, A.; Näslund, E.; Rössner, S.; Zierath, J. R.; Arner, P. // Diabetologia;Aug2002, Vol. 45 Issue 8, p1128 

    Aim/hypothesis. We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women. Methods. Glucose transport and insulin signalling were...

  • Translocation of IRS-1 to Cytosol Attenuates Insulin-Stimulated Glucose Transport without Affecting PI3-Kinase Activity. Kawahara, Junko; Usui, Isao; Haruta, Tetsuro; Kanatani, Yukiko; Hiratani, Kazuyuki; Takano, Atsuko; Uno, Tatsuhito; Iwata, Minoru; Kobayashi, Masashi; Tobe, Kazuyuki // Open Diabetes Journal;2010, Vol. 3, p14 

    IRS-1 is a major substrate for insulin receptor tyrosine kinase. It is reported that intracellular translocation of serine-phosphorylated IRS-1 from low density microsome (LDM) fraction to cytosol attenuates its ability to transmit insulin signaling to the downstream molecules. In this study, we...

  • Developmental biology: Gender benders. Koopman, Peter // Nature;11/20/2003, Vol. 426 Issue 6964, p241 

    A painstaking triple-gene-knockout study has revealed a crucial role for insulin receptors in male sexual development.

  • Glucose-dependent promotion of insulin release from mouse pancreatic islets by the insulin-mimetic compound L-783,281. Westerlund, Johanna; Wolf, Bryan A.; Bergsten, Peter // Diabetes;Feb2002 Supplement, Vol. 51, pS50 

    An insulin-mimetic compound (L-783,281) was used in an attempt to determine the role of the beta-cell insulin receptor (IR) on insulin release. Islets were isolated from C57Bl/6j mice and cultured for 1 to 4 days. Insulin release from individual islets perifused in the presence of 3 mmol/l...

  • Role of IRS-2 in insulin and cytokine signalling. Lane, William S.; Pierce, Jacalyn H. // Nature;9/14/1995, Vol. 377 Issue 6545, p173 

    Reports the discovery of a second IRS-signalling protein for insulin and cytokines. Role in gene expression and mitogenesis.

  • Oral Insulin-Mimetic Compounds That Act Independently of Insulin. García-Vicente, Silvia; Yraola, Francesc; Marti, Luc; González-Muñoz, Elena; García-Barrado, María José; Cantó, Carles; Abella, Anna; Bour, Sandy; Artuch, Rafael; Sierra, Cristina; Brandi, Nuria; Carpéné, Christian; Moratinos, Julio; Camps, Marta; Palacín, Manuel; Testar, Xavier; Gumà, Anna; Albericio, Fernando; Royo, Miriam; Mian, Alec // Diabetes;Feb2007, Vol. 56 Issue 2, p486 

    The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's...

  • FUNCTIONAL GENOMICS: Insulin ? meet the family. Patterson, Mark // Nature Reviews Genetics;Apr2001, Vol. 2 Issue 4, p243 

    Discusses research being done on the regulation of insulin receptor DAF-2 signaling by human insulin and ins-1, one of the Caenorhabditis elegans genes. Reference to a study by Pierce et al; Candidates for endogenous insulin signals in Caenorhabditis elegans.

  • GYM GEM. Stoppani, Jim // Joe Weider's Muscle & Fitness;Dec2006, Vol. 67 Issue 12, p216 

    This article discusses the nutritional benefits of the herb Gymnema sylvestre. The herb helps increase insulin sensitivity, and increases insulin secretion to the pancreas. More insulin can lead to a greater anabolic response, and can increase muscle growth after workouts. The author advises...

  • Lack of Arg972 Polymorphism in the IRS1 Gene in Parakanã Brazilian Indians. Bezerra, Rosângela M. N.; Chadid, Thiago T.; Altemani, Claúdia M.; Sales, Teresa S. I.; Menezes, Raimundo; Soares, Manoel C. P.; Saad, Sara T. O.; Saad, Mario J. A. // Human Biology;Feb2004, Vol. 76 Issue 1, p147 

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly →Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics