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Mediators of Inflammation
Volume 2013 (2013), Article ID 429207, 8 pages
http://dx.doi.org/10.1155/2013/429207
Research Article

Metformin Inhibits Expression and Secretion of PEDF in Adipocyte and Hepatocyte via Promoting AMPK Phosphorylation

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, China

Received 18 June 2013; Revised 7 August 2013; Accepted 9 September 2013

Academic Editor: Magdalena Klink

Copyright © 2013 Shumin Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro. Methods. SD rats were divided into normal control group, high fat group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and HepG2 cells were established and then treated with metformin and inhibitor of AMP activated protein kinase (AMPK). Results. In vivo, the HF group showed increased serum PEDF which is negatively correlated with insulin sensitivity, while the MET group revealed decreased serum PEDF and downregulated PEDF expression in fat and liver, concomitant with significantly improved IR. In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake. Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated. Conclusions. Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.