HNF4α controls beta cell proliferation mass process induced by dexamethasone

Prêmio José Antunes Rodrigues ( mestrado ) Diabetes Mellitus (DM) is a pathology of multiple etiology characterized by a chronic hyperglycemia panorama and it is considered a major public health care problem. Type 1 diabetes results from the massive β cell depletion, type 2 occurs the partial depletion of these β cells being associated sometimes with insulin resistance (IR) or not. Insulin resistance is responsible for the increase of the β cell mass and for triggering the pancreatic plasticity as well. Thus, the insulin resistance effect creates a compensation form on β cells, and this effect, therefore, considered a target of studies that have therapeutic aim to treat DM. Is well known that pancreatic plasticity also can be affected by specific transcription factors such as super expression or its absence like PDX1 and HNF4α. The HNF4α is a essential transcription factor to β cell, because it regulates the protein expression that participates in glucose metabolism, as well on gene expression of insulin secretion, also participating in the pancreatic plasticity process. HNF4α controls the β cell mass increase in response to stress (e.g. pregnancy) through the activation of the two kinase pathways regulated by extracellular signal ERK-ST5. It is also known that HNF4α regulates ERK and this control expression and nuclear translocation of the transcription factor NeuroD and the PDX1 activation, essentials to the development and survival of the pancreatic islet. Pancreatic plasticity mechanisms allow non - β cells to turn into β-like cells to supply an insulin increase demand like in IR. The pancreatic plasticity is commonly be assimilated with the increased β cell mass because both processes increase β cell numbers.