β cells can be generated from cytokeratin 5-positive cells after cerulein-induced pancreatitis in adult mice

Clinical studies have revealed that some patients will develop glucose tolerance dysfunction after recovering from acute pancreatitis (AP), which indicated the importance of investigating the potential therapies for restoration of islet β cell function. Cytokeratin 5 (Krt5)-positive cells are considered to function as stem or progenitor cells in the regeneration of lung and salivary gland following injury. In the present study, AP was induced by six hourly intraperitoneal injections of 100 μg/kg cerulein for 4 consecutive days in adult mice, in order to determine the role of Krt5-positive cells in pancreatic regeneration, especially in the restoration of β cell function and the underlying mechanisms. Results showed that glucose homeostasis were deteriorated partly during the recovery process after AP. Furthermore, clusters of Krt5-positive cells were significantly increased in the damaged pancreas marked by inflammatory cells infiltration and acinar cell eradication. In addition, cells co-labelling insulin and Krt5 were found in the injured region after cerulein administration, part of these cells were immunopositive for GLUT2. Taken together, our data demonstrated that Krt5-expressing cells could be involved in the natural pancreas self-healing process and the renewal of β cells after AP in adult mice. It is promising that promoting conversion of Krt5-expressing cells into functional β cells may be a novel method to mitigate the development of diabetes mellitus after AP in vivo.