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Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine, by insulin

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Tan, Bee K., Adya, Raghu, Shan, Xiaoye, Syed, Farhatullah, Levandowski, Krzysztof C., O'Hare, J. Paul and Randeva, Harpal S.. (2009) Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine, by insulin. Diabetes Care, Vol.32 (No.1). pp. 129-131. ISSN 0149-5992

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Official URL: http://dx.doi.org/10.2337/dc08-1236

Abstract

OBJECTIVE - Lipocalin-2, a novel adipokine, has been shown to be elevated in obese, insulin-resistant, and diabetic Subjects. We therefore sought to study the ex vivo and in vivo effects of insulin on lipocalin-2 levels in humans. RESEARCH DESIGN AND METHODS - We investigated the in vivo effects of insulin (hyperinsulinemia) on circulating lipocalin-2 levels by enzyme-linked immunosorbent assay via a prolonged insulin-glucose infusion. The ex vivo effect of insulin on adipose tissue lipocalin-2 protein production and secretion into conditioned media was assessed by Western blotting and enzyme-linked immunosorbent assay, respectively. RESULTS - Hyperinsulinemic induction in human subjects significantly increased circulating lipocalin-2 levels (P < 0.01). Also, in omental adipose tissue explants, insulin caused a significant dose-dependent increase in lipocalin-2 protein production and secretion into conditioned media (P < 0.05, P < 0.01, respectively); these effects were negated by both phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase inhibitions. CONCLUSIONS - Lipocalin-2 is upregulated by insulin via phosphatidylinositol 3-kinasc and mitogen-activated protein kinase signaling pathways.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Adipose tissues, Obesity -- Pathophysiology, Insulin resistance
Journal or Publication Title: Diabetes Care
Publisher: American Diabetes Association
ISSN: 0149-5992
Date: January 2009
Volume: Vol.32
Number: No.1
Number of Pages: 3
Page Range: pp. 129-131
Identification Number: 10.2337/dc08-1236
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: General Charities of the City of Coventry
References: 1. Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 365:1415– 1428, 2005 2. Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556, 2004 3. Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED: The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 56:2533–2540, 2007 4. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, Xu A: Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53: 34–41, 2007 5. Lewandowski K, Randeva HS, O’Callaghan CJ, Horn R, Medley GF, Hillhouse EW, Brabant G, O’Hare P: Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin. Clin Endocrinol (Oxf) 54:533–539, 2001 6. Tan BK, Chen J, Lehnert H, Kennedy R, Randeva HS: Raised serum, adipocyte and adipose tissue Retinol-Binding Protein 4 (RBP4) in overweight women with polycystic ovary syndrome: effects of gonadal and adrenal steroids. J Clin Endocrinol Metab 92:2764–2772, 2007
URI: http://wrap.warwick.ac.uk/id/eprint/28769

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