Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes

Diabetes Mellitus is currently affecting more than 425 million people worldwide, among which over 90 % of the cases belong to type 2 diabetes. The number is growing quickly every year. Together with its many complications, the disease is causing tremendous social and economic burden and is classified as one of the leading causes of high morbidity and mortality rate. Residing in the islets of Langerhans, pancreatic beta cell serves as a central mediator in glucose homeostasis through secreting insulin, the only hormone that could reduce glucose level in the body, into the blood. Abnormality in pancreatic beta cell is generally considered as the fundamental reason which is responsible for the development of diabetes. Evidence shows that beta cell mass is greatly reduced in the biopsy of type 2 diabetic patients. Since then, large amount of research was conducted in order to decipher the molecular mechanisms behind the phenotype above and enormous progression has been made. The aim of this review is to summarize and provide a rudimentary molecular road map for beta cell mass reduction from the aspects of apoptosis and dedifferentiation based on recent research advances. Hopefully, this review could give the community some enlightenment for the next-step research and, more importantly, could provide avenues for developing novel and effective therapies to restrain or reverse beta cell loss in type 2 diabetes in the clinic.