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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 > Translational & Systems Medicine > 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
Official 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 (GCCC)
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