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Role of pancreatic-derived factor in type 2 diabetes: evidence from pancreatic β cells and liver

Authors

  • Chunjiong Wang,

    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing 100191, China
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  • Brant R Burkhardt,

    1. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA
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  • Youfei Guan,

    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing 100191, China
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  • Jichun Yang

    Corresponding author
    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing 100191, China
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J Yang, Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. E-mail: yangj@bjmu.edu.cn, Phone: +86-10-82805027.

Abstract

Pancreatic-derived factor (PANDER) is a cytokine-like protein that is highly expressed in pancreatic islets. In vitro, PANDER pretreatment or viral-mediated overexpression promotes apoptosis of islet β cells. Under conditions of insulin resistance, chronic hyperglycemia potently activates PANDER expression and stimulates the cosecretion of insulin and PANDER in β cells. PANDER binds to the liver cell membrane and induces insulin resistance, resulting in increased gluconeogenesis. Recently, PANDER was found to be expressed in rodent and human liver, and its expression is increased in the liver of diabetic mice and rats. Hepatic overexpression of PANDER promotes lipogenesis in the liver and induces insulin resistance in C57BL/6 mice, whereas the inactivation of hepatic PANDER markedly reduces steatosis, insulin resistance, and hyperglycemia in db/db mice. PANDER deficiency protects mice from high-fat-diet-induced hyperglycemia by decreasing gluconeogenesis in the liver. In summary, PANDER plays an important role in the progression of type 2 diabetes by negatively regulating islet β-cell function and insulin sensitivity in the liver.

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