**4. Concluding remarks**

It is well known that ARNT/HIF-1β plays a role in the cellular responses to hypoxia, however recent research has demonstrated a broader role for this transcription factor in maintaining glucose and lipid homeostasis in type 2 diabetics. It is now clear that a significant decrease in ARNT/HIF-1β gene expression in both the pancreatic beta-cells and the liver cells is deleterious and can result in T2D. Conversely, targeted disruption of ARNT/HIF-1β gene expression in the adipocytes followed by treatment of mice with a high fat diet improves insulin sensitivity and decreases adiposity (Jiang *et al.*, 2011). A central role for ARNT/HIF-1β in the regulation of key genes involved in glucose sensing, GSIS and insulin signaling in rodents as well in human islets suggest it plays an important role in maintaining normal beta-cell function. Current studies support the idea that ARNT/HIF-1β could act as an upstream regulator of many of the key genes involved in glucose and lipid homeostasis. Clearly, the transcriptional network regulated by ARNT/HIF-1β and genes that are under direct or indirect control of this transcription factor is very broad and hence any change in the regulation of ARNT/HIF-1β may have an impact on many signaling pathways. The fact that ARNT/HIF-1β is a binding partner for several other Per/ARNT/Sim transcription factor family members like HIF-1α, HIF-2α, HIF-3α and AhR makes it a significant member of this family of transcription factors. Improving our understanding of the beta-cell transcription factors, establishing their mechanism of action and hierarchy and finding ways to regulate their expression could prove beneficial in developing novel tools to prevent or correct beta-cell dysfunction in T2D.

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