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Control of insulin sensitivity through transcriptional co-factors: implications for type II diabetes therapy

Final Activity Report Summary - INSULIN RESISTANCE (Control of insulin sensitivity through transcriptional co-factors: implications for type II diabetes therapy)

Research has been focused on the transcriptional control of metabolism and its contribution to the development of metabolic diseases such as type II diabetes, atherosclerosis and cancer cachexia. The development of resistance against the pancreatic hormone insulin is the common hallmark of these disorders and represents an increasingly important threat to public health worldwide.

By analysing signal-dependent transcription factor action, we have aimed to ultimately decipher the molecular basis for insulin resistance and the subsequent defects in energy homeostasis.

In this respect, our work has been able to identify novel transcriptional co-factor complexes as integrative sites for dietary, inflammatory, and hormonal pathways, thereby impacting both pro-inflammatory and metabolic programs in critical target tissues and determining systemic energy homeostasis.

Furthermore, the Marie Curie Excellence team has unravelled an as-yet unappreciated involvement of inflammatory mediators in the control of systemic energy balance through the modulation of adipocyte progenitor cell fate decisions. Together, our studies have been able to establish novel transcriptional signalling pathways and mechanisms in the integration of metabolism and inflammation, thereby substantially expanding the understanding of this increasingly important aspect of insulin resistance and its associated disorders. Individual pathways components will now help to improve therapeutic options in the treatment of chronic inflammatory, insulin resistant conditions such as cancer cachexia and the Metabolic Syndrome.