**10. Transcription factors**

Another stratification of regulation besides glucose signaling and mRNA expression is at the level of transcription factors. These play a central role in regulating gene expression by binding to specific consensus sequences, or cis-elements, within promoter regions [24]. Transcription factors are proteins that can be targets of modifications when they respond to cellular stimuli. This will affect their stability, activity, intracellular distribution, and interaction with other proteins [25]. One of these stimuli is insulin resistance, which affects many organs, mainly the liver, pancreas, adipose tissue, and muscle [26, 27].

Illustrating the power of transcription factors, pancreatic acinar cells can be reprogrammed to produce, process, and secrete insulin when forced to express the transcription factors Pdx-1, MafA, and Ngn3 [28].

### *Diabetes and Epigenetics DOI: http://dx.doi.org/10.5772/intechopen.104653*

Cellular differentiation processes can also be negatively impacted by gene expression [8]. For example, the deletion of pancreatic and duodenal homeobox 1 (PDX-1) from postnatal islets results in phenotypic loss of the β-cells. The Pdx-1 protein is a transcription factor responsible for the development of α and β-cells [8]. A second proposed explanation for the loss of β-cell phenotype is that there is an increase in α cells in the pancreatic islets due to a lack of Pdx-1 transcriptional processes, which convert α cells to β-cells [8]. This process would produce an overall imbalance between α and β-cells; hence the β-cells would ultimately be fewer, but it is unclear whether the loss of the β-cell phenotype was due to lack of Pdx-1 or lack of α to β-cell conversion [29].

Even more starkly, mutation in both PDX-1 and PTF1A results in pancreatic agenesis [8]. PTF1A is a gene that is a component of transcription factor 1 complex (PTF1) in the pancreas and encodes a protein that functions in embryonic pancreatic development. It is crucial and determines if cells in the pancreatic buds go on either towards pancreatic organogenesis or return to duodenal fates [18, 30].

Although we see that transcription factors are powerful effectors of cellular behavior, there are deeper layers than this, namely epigenetic, which we will begin to cover in more detail.
