Ex Vivo and In Vivo Regulation of Lipocalin-2, a Novel Adipokine, by Insulin
- Bee K. Tan, MBBS, PHD1,
- Raghu Adya, MBBS, MSC1,
- Xiaoye Shan, BSC1,
- Farhatullah Syed, MSC, PHD1,
- Krzysztof C. Lewandowski, MRCP, MD12,
- John P. O'Hare, FRCP, MD1 and
- Harpal S. Randeva, FRCP, MD, PHD1
- 1Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.
- 2Department of Endocrinology and Metabolic Diseases, The Medical University of Lodz and Polish Mother's Memorial Research Institute, Lodz, Poland
- Corresponding author: Harpal S. Randeva, harpal.randeva{at}warwick.ac.uk
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 inhibitors.
CONCLUSIONS—Lipocalin-2 is upregulated by insulin via phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways.
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 13 October 2008.
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- Accepted September 30, 2008.
- Received July 5, 2008.
- DIABETES CARE
