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


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.
Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.
Bee K
BK
Tan
Raghu
R
Adya
Xiaoye
X
Shan
Farhatullah
F
Syed
Krzysztof C
KC
Lewandowski
John P
JP
O'Hare
Harpal S
HS
Randeva
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015992:Body Mass Index; D002940:Circadian Rhythm; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D015398:Signal Transduction; D055815:Young Adult
D000209:Acute-Phase Proteins; D007328:Insulin; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases