Endocrinological characterization of pancreatic ducts in HFD and HGD fed mice

Our previous findings show that insulin-produced cells are found in human pancreatic ducts. However, the underlying molecular mechanism of transdifferentiation in pancreatic ductal cells is not yet totally uncovered. High-fat diet (HFD) and high-glucose diet (HGD) fed mice were subjected to the biochemical tests in sera. And the pancreatic samples were used for immunostaining and immunoblotting assays, respectively. These serological findings showed that fasting blood glucose, insulin, blood lipids (triglyceride, total cholesterol), liver functional enzymes (glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase) were increased in HFD fed mice. Immunostaining observations showed that insulin protein was positively expressed in pancreatic islets and ducts, characterized with elevated immunoreactive cells of insulin, neurogenin-3, poly (ADP-ribose) polymerase (PARP), and reduced F-box/WD repeat-containing protein 7-positive cells in pancreatic islets and ducts of HFD and HGD fed mice. Interestingly, immunoblotting assays suggested that intrapancreatic expressions of insulin, Krüppel-like Factor 2, PARP, p42/44MAPK proteins were upregulated in HFD and HGD exposed mice, while Fbxw7 protein content in pancreas samples were reduced. Taken together, the current findings reveal that there may be potential transdifferentiation of insulin-producing cells in pancreatic ducts through inducing a pathway of intracellular Fbxw7 ubiquitination.