PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells

Yang, Jichun; Wang, Chunjiong; Li, Jing; Burkhardt, Brant R.; Robert-Cooperman, Claudia E.; Wilson, Camella; Gao, Zhiyong; Wolf, Bryan A.

doi:10.1016/j.febslet.2009.08.008

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Volume 583, Issue 18 , Pages 3009-3015, 17 September 2009

PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cells

Edited by Robert Barouki

Jichun Yang
- Department of Physiology and Pathophysiology, Peking University School of Basical Medicine, Beijing 100191, PR China
- Corresponding authors. Addresses: 38 Xueyuan Road, Beijing 100191, PR China (J. Yang), 5135 Main, 34th Street and Civic Center Blvd., Philadelphia, PA 19104-4399, USA (B.A. Wolf).
Chunjiong Wang
- Department of Physiology and Pathophysiology, Peking University School of Basical Medicine, Beijing 100191, PR China
Jing Li
- Department of Physiology and Pathophysiology, Peking University School of Basical Medicine, Beijing 100191, PR China
Brant R. Burkhardt
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Claudia E. Robert-Cooperman
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Camella Wilson
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Zhiyong Gao
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Bryan A. Wolf
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- Corresponding authors. Addresses: 38 Xueyuan Road, Beijing 100191, PR China (J. Yang), 5135 Main, 34th Street and Civic Center Blvd., Philadelphia, PA 19104-4399, USA (B.A. Wolf).

Received 8 June 2009; received in revised form 3 August 2009; accepted 6 August 2009. published online 14 August 2009.

Abstract

PANDER is a cytokine co-secreted with insulin from islet β-cells. To date, the physiological function of PANDER remains largely unknown. Here we show that PANDER binds to the liver membrane by ¹²⁵I-PANDER saturation and competitive binding assays. In HepG2 cells, pre-treatment with PANDER ranging from 4pM to 4nM for 8h resulted in a maximal inhibition of insulin-stimulated activation of insulin receptor and insulin receptor substrate 1 by 52% and 63%, respectively. Moreover, PANDER treatment also reduced insulin-stimulated PI3K and pAkt levels by 55% and 48%, respectively. In summary, we have identified the liver as a novel target for PANDER, and PANDER may be involved in the progression of diabetes by regulating hepatic insulin signaling pathways.