Regulation of pancreatic beta-cell mass and its importance for antidiabetic therapies

Furthermore, beta-cell mass is subject to complex hormonal regulation.It is well-known that thyroid hormones reduce beta-cell mass via apoptosis, whereas glucocorticoids increase it through proliferation-a pattern observed in all mammals, including humans [17,18].The well-documented expansion of beta-cell mass during pregnancy also supports this view [19].The proliferative capacity of beta-cells is particularly relevant because it can not only counteract the deterioration of the metabolic state during the pre-diabetic phase but may also support therapeutic efforts to restore metabolic control after diabetes onset.On the other hand, it is important to consistently mitigate any increased workload on the beta-cells such as caused by obesity or autoimmune attack since it always carries the risk of deteriorating beta-cell function and reducing beta-cell mass.Results from animal studies indicate that the propensity for compensatory beta-cell proliferation increases when beta-cell mass has declined due to disease [20].As therapeutic options become increasingly diverse, this issue will gain significance in the future.In particular, the question arises as to whether pharmacotherapeutic interventions can contribute to restoring reduced beta-cell mass beyond endogenous, genetically driven proliferation.After all, both T1DM and T2DM are associated with a progressive beta-cell loss over time [21][22][23][24].In this context, determining the optimal timing for such therapeutic interventions is of crucial importance.