Regeneration of pancreatic beta-cell mass for the treatment of diabetes

Abstract

Introduction: The study of the endocrine compartment of the pancreas (the islets of Langerhans) is of great translational interest, as strategies aimed at restoring its mass could become therapies for glycemic dysregulation in type 1 and 2 diabetes mellitus, drug-related diabetes following diabetogenic therapies or hyperglycemic disturbances following the treatment of cancer and nesidioblastosis. Such strategies generally fall under one of the ‘three Rs,’ namely, replacement (islet transplantation and stem cell differentiation), reprogramming (chiefly from the exocrine compartment of the pancreas) and regeneration (replication and induction of endogenous stem cells).

Areas covered: This expert opinion focuses on the latter, as islets are known to regenerate under specific circumstances of physiological (e.g., pregnancy), pathological (e.g., obesity, hyperglycemia, mutations in the glucose-sensing pathway) or experimental (e.g., partial pancreatectomy, cellophane wrapping, partial duct ligation) nature. This review presents the different models of pancreatic regeneration, which encompass the replication of existing beta-cells, reversible epithelial-to-mesenchymal transition and the reactivation of resident stem cells.

Expert opinion: Rather than a set mechanism, the pancreas appears to possess a wide range of facultative regeneration pathways. These are discussed in the context of the development of potential strategies aimed at restoring beta-cell function in insulin-dependent diabetes.

Keywords::

• beta-cell replication
• glucokinase-activating mutations
• islet regeneration
• pregnancy

Acknowledgments

The authors acknowledge the help of AL Cuesta Muñoz (Hospital Universitario Carlos Haya, Málaga, Spain) for his critical review of the manuscript.