Reversing pancreatic & beta;-cell dedifferentiation in the treatment of type 2 diabetes

Diabetes: Regression of insulin-producing & beta;-cells in the pancreasTherapies aimed at preventing or reversing the regression of pancreatic insulin-producing cells could restore healthy sugar metabolism in individuals with type 2 diabetes. Jinsook Son and Domenico Accili from Columbia University, New York, USA, review how cellular stress and metabolic dysfunction can prompt & beta;-cells in the pancreas to 'dedifferentiate', a process by which the specialized insulin-making cells transform into a more primitive state. The same triggers can also cause & beta;-cells to 'trans-differentiate' into other cell types. In both cases, the pancreas loses & beta;-cells, leading to compromised insulin production and impaired glucose metabolism. By understanding the underlying molecular mechanisms and signaling pathways involved in these processes, researchers hope to develop targeted therapies to inhibit or reverse the regression of pancreatic & beta;-cells. The maintenance of glucose homeostasis is fundamental for survival and health. Diabetes develops when glucose homeostasis fails. Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic & beta;-cell failure. The failure of & beta;-cells to compensate for insulin resistance results in hyperglycemia, which in turn drives altered lipid metabolism and & beta;-cell failure. Thus, insulin secretion by pancreatic & beta;-cells is a primary component of glucose homeostasis. Impaired & beta;-cell function and reduced & beta;-cell mass are found in diabetes. Both features stem from a failure to maintain & beta;-cell identity, which causes & beta;-cells to dedifferentiate into nonfunctional endocrine progenitor-like cells or to trans-differentiate into other endocrine cell types. In this regard, one of the key issues in achieving disease modification is how to reestablish & beta;-cell identity. In this review, we focus on the causes and implications of & beta;-cell failure, as well as its potential reversibility as a T2D treatment.

Automated summary

Diabetes: Regression of insulin-producing β-cells in the pancreas. Therapies aimed at preventing or reversing the regression of pancreatic insulin-producing cells could restore healthy sugar metabolism in individuals with type 2 diabetes. By understanding the molecular mechanisms and signaling pathways involved, researchers hope to develop targeted therapies to inhibit or reverse the regression of pancreatic β-cells.