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, MD1,2,
- John P O'Hare, FRCP, MD1 and
- Harpal S Randeva, FRCP, MD, PhD (Harpal.Randeva{at}warwick.ac.uk)1
- 1Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- 2Department of Endocrinology and Metabolic Diseases, The Medical University of Lodz and Polish Mother's Memorial Research Institute, Lodz, Poland.
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 ELISA via a prolonged insulin-glucose infusion. The ex vivo effect of insulin on adipose tissue (AT) Lipocalin-2 protein production and secretion into conditioned media were assessed by western blotting and ELISA, respectively.
Results Hyperinsulinemic induction in human subjects significantly increased circulating Lipocalin-2 levels (P < 0.01). Also, in omental AT 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 PI3K and MEK inhibitors.
Conclusions Lipocalin-2 is up-regulated by insulin via PI3K and MAPK signalling pathways.
Footnotes
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- Received July 5, 2008.
- Accepted September 30, 2008.
- Copyright © American Diabetes Association
