The impact of b-cell Replication on Diabetes Therapy

Younes S

Published on: 2024-03-31

Abstract

Type 2 diabetes is characterized by a decrease in the mass of b-cells, which is attributed to the failure of b-cell compensation. It is crucial to understand the mechanism behind the adaptive increase in b-cell mass in vivo in order to develop a cure for diabetes. The signaling pathways mediated by insulin and the insulin receptor (IR) have been found to play a significant role in promoting compensatory b-cell proliferation in response to chronic insulin resistance. However, there is still debate regarding the requirement of IR for compensatory b-cell proliferation in certain situations. It is possible that IR may act as a scaffold for the signaling complex, independent of its ligand. Furthermore, the pathway involving the forkhead box protein M1/polo-like kinase 1/centromere protein A has been identified as a key player in adaptive b-cell proliferation during various conditions such as diet-induced obesity, hyperglycemia, pregnancy, aging, and acute insulin resistance. Recent studies have also shown that the interaction between islets and adipose tissue, as well as the liver, through humoral factors contributes to adaptive b-cell proliferation. Notably, this response is particularly observed under conditions of acute insulin resistance, regardless of the IR/insulin signal, and relies on the forkhead box protein M1/polo-like kinase 1/centromere protein a pathway. However, a significant challenge in using b-cells for the treatment of human diabetes is the difference between human and rodent islets. This review focuses on the signaling pathways that regulate adaptive b-cell proliferation, considering the aforementioned issues, with the goal of advancing diabetes treatment.