TITLE

Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes

AUTHOR(S)
Takano, Atsuko; Haruta, Tetsuro; Iwata, Minoru; Usui, Isao; Uno, Tatsuhito; Kawahara, Junko; Ueno, Eiichi; Sasaoka, Toshiyasu; Kobayashi, Masashi; Takano, A; Haruta, T; Iwata, M; Usui, I; Uno, T; Kawahara, J; Ueno, E; Sasaoka, T; Kobayashi, M
PUB. DATE
August 2001
SOURCE
Diabetes;Aug2001, Vol. 50 Issue 8, p1891
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110(CAAX)) or Akt activation stimulated by platelet-derived growth factor. Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. These results indicate that cellular insulin resistance induced by chronic GH treatment in 3T3-L1 adipocytes is caused by uncoupling between activation of PI 3-kinase and its downstream signals, which is specific to the insulin-stimulated PI 3-kinase pathway. This effect of GH might result from the altered subcellular distribution of IRS-1-associated PI 3-kinase.
ACCESSION #
4969424

 

Related Articles

  • Fructose sugar makes maturing human fat cells fatter and less insulin-sensitive.  // Food Engineering & Ingredients;Jun2010, Vol. 35 Issue 3, p26 

    The article reports on the study lead by Georgina Coade of the University of Bristol in Great Britain that shows that fructose sugar present during maturation process of fat cells can make these cells mature into fat cells and less insulin-sensitive which raises risk of heart disease and diabetes.

  • Safety of the insulin tolerance test. Galloway, P.J.; McNeill, E.; Paterson, W.F.; Donaldson, M.D.C. // Archives of Disease in Childhood;Oct2002, Vol. 87 Issue 4, p354 

    Concerns have been raised about the hazards of the insulin tolerance test (ITT), used to measure growth hormone secretion. In Glasgow, we continue to use this test, adhering to a strict protocol. A review of outcome over a 10 year period (1989-99), during which 550 ITTs were performed, was...

  • Common Genetic Variation in the SERPINF1 Locus Determines Overall Adiposity, Obesity-Related Insulin Resistance, and Circulating Leptin Levels. B�hm, Anja; Ordelheide, Anna-Maria; Machann, J�rgen; Heni, Martin; Ketterer, Caroline; Machicao, Fausto; Schick, Fritz; Stefan, Norbert; Fritsche, Andreas; H�ring, Hans-Ulrich; Staiger, Harald // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    Objective: Pigment epithelium-derived factor (PEDF) belongs to the serpin family of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance....

  • Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes. Yuchang Fu; Liehong Luo; Nanlan Luo; Garvey, W. Timothy // Nutrition & Metabolism;2006, Vol. 3, p28 

    Resistin is secreted from adipocytes, and high circulating levels have been associated with obesity and insulin resistance. To investigate whether resistin could exert autocrine effects in adipocytes, we expressed resistin gene in 3T3-L1 fibroblasts using a lentiviral vector, and selected...

  • The Impact Of Adiposity And Insulin Resistance On Endothelial Function In Middle-Aged Subjects. Zhu, Lvyun; Liu, Kunshen // Internet Journal of Cardiovascular Research;2002, Vol. 1 Issue 1, p13 

    Objectives: To investigate the relationship between adiposity, adipose distribution,insulin resistance (IR) and vascular endothelial function. Methods: Flow-mediated endothelium-dependent dilation (EDD), body mass index (BMI), waist circumference, waist hip ratio and IR index (HOMA-IR) were...

  • Decreased in situ insulin receptor dephosphorylation in hyperglycemia-induced insulin resistance in rat adipocytes. Tang, Shangguo; Le-Tien, Hoang; Goldstein, Barry J.; Shin, Phillip; Lai, Robert; Fantus, I. George; Tang, S; Le-Tien, H; Goldstein, B J; Shin, P; Lai, R; Fantus, I G // Diabetes;Jan2001, Vol. 50 Issue 1, p83 

    The regulation of insulin receptor (IR) tyrosine (tyr) phosphorylation is a key step in the control of insulin signaling. Augmented IR tyr dephosphorylation by protein tyrosine phosphatases (PTPs) may contribute to insulin resistance. To investigate this possibility in hyperglycemia-induced...

  • Differential effects of rosiglitazone on skeletal muscle and liver insulin resistance in A-ZIP/F-1 fatless mice. Kim, Jason K.; Fillmore, Jonathan J.; Gavrilova, Oksana; Chao, Lily; Higashimori, Takamasa; Choi, Hyejeong; Hyejeong Choi; Kim, Hyo-Jeong; Hyo-Jeong Kim; Chunli Yu; Yu, Chunli; Yan Chen; Chen, Yan; Xianqin Qu; Qu, Xianqin; Haluzik, Martin; Reitman, Marc L.; Shulman, Gerald I. // Diabetes;Jun2003, Vol. 52 Issue 6, p1311 

    To determine the role of adipocytes and the tissue-specific nature in the insulin sensitizing action of rosiglitazone, we examined the effects of 3 weeks of rosiglitazone treatment on insulin signaling and action during hyperinsulinemic-euglycemic clamps in awake A-ZIP/F-1 (fatless),...

  • Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Dietze, Daniela; Koenen, Marlis; Röhrig, Karin; Horikoshi, Hiroyoshi; Hauner, Hans; Eckel, Jürgen; Röhrig, Karin; Eckel, Jürgen // Diabetes;Aug2002, Vol. 51 Issue 8, p2369 

    Adipocyte factors play a major role in the induction of insulin resistance in skeletal muscle. To analyze this cross-talk, we established a system of co-culture of human fat and skeletal muscle cells. Cells of three muscle donors were kept in co-culture with cells of various fat cell donors, and...

  • Anthocyanins Show Promise for Obesity. Ninger, Laura J. // Life Extension;Aug2008, Vol. 14 Issue 8, p20 

    The article offers information about anthocyanins, the colorful antioxidant pigments found in fruits and vegetables. According to a study, it helps regulate adipocyte function and obesity. Adipocyte or fat cell dysfunction promotes obesity and is a major risk for metabolic syndrome and insulin...

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