Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, China.
Nutr Rev. 2012 Feb;70(2):100-6. doi: 10.1111/j.1753-4887.2011.00457.x.
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.
胰腺衍生因子（PANDER）是一种细胞因子样蛋白，在胰岛中高度表达。在体外，PANDER 预处理或病毒介导的过表达促进胰岛β细胞凋亡。在胰岛素抵抗的情况下，慢性高血糖强烈激活 PANDER 的表达，并刺激β细胞中胰岛素和 PANDER 的共分泌。PANDER 与肝细胞膜结合并诱导胰岛素抵抗，导致肝糖异生增加。最近，发现 PANDER 在啮齿动物和人类肝脏中表达，并在糖尿病小鼠和大鼠的肝脏中表达增加。肝过量表达 PANDER 促进肝脏中的脂肪生成，并诱导 C57BL/6 小鼠胰岛素抵抗，而肝 PANDER 的失活则显著减少 db/db 小鼠的脂肪变性、胰岛素抵抗和高血糖。PANDER 缺乏通过减少肝脏中的糖异生来保护小鼠免受高脂肪饮食引起的高血糖。总之，PANDER 通过负向调节胰岛β细胞功能和肝脏胰岛素敏感性，在 2 型糖尿病的进展中发挥重要作用。
