Pancreatic-derived factor (PANDER, FAM3B) is a PANDER is a 235-amino acid member of the FAM3 family of cytokine molecules that is highly expressed in pancreatic islets. It is secreted from both pancreatic α and β-cells, and appears to colocalize with both insulin and glucagon. In vitro, PANDER pretreatment or viral-mediated overexpression promotes apoptosis of islet β cells and inhibits insulin secretion. 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. 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. PANDER knock out mice on high-fat diet are glucose intolerant yet resistant to fasting hyperglycemia and hyperinsulinemia. RNA-mediated knockdown of hepatic PANDER significantly attenuated steatosis. Hepatic PANDER silencing also attenuated insulin resistance and hyperglycemia in db/db mice. In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased Forkhead box protein O1 (FOXO1) expression, and suppressed insulin-stimulated Akt activation and FOXO1 inactivation. Moreover, FOXO1 overexpression increased PANDER expression in cultured hepatocytes and mouse livers IFN-γ has been shown to regulate PANDER expression in mouse islets in a dose- and time-dependent manner, suggesting that PANDER may be involved in IFN-γ-mediated apoptosis of islet β cells Monocyte chemotactic protein-1 induced PANDER mRNA transcription and protein synthesis in MIN6 cells and islets.
- References to Pancreatic-Derived Factor (PANDER, FAM3B)