ARNT: a Novel Target for Treatment of Diabetes

Description: The invention is based on the discovery of a new target, not previously known to be linked to diabetes. Microarray analysis of human pancreatic islets from people with Type 2 diabetes compared to controls with normal glucose tolerance showed that the transcription factor aryl hydrocarbon nuclear receptor translocator (ARNT) was down-regulated in the diabetic individuals. This factor was expressed in all of the control individuals but expression was not detected in microarray analysis of samples from any of the diabetic subjects: using RT-PCR, expression of the factor in diabetic subjects was 10% of that in control subjects. Beta-cell specific knockout mice lacking the gene encoding this transcription factor developed beta cell dysfunction and diabetes. In vitro experiments confirm the changes in glucose-responsive insulin secretion and mRNA levels seen in vivo to result from decreased levels of this transcription factor. Clinical & Commercial Utility: The invention provides a novel target for drug development and therapeutic intervention against both Type 1 and Type 2 diabetes. Agents that might enhance expression or activity of ARNT, including several that are known, could be used to treat diabetes. The invention includes methods of treating diabetes by increasing the activity or level of the factor; methods of drug screening against this target, and methods of detecting the risk, predisposition, or presence of diabetes in a subject by measuring levels of the transcription factor
A U.S. patent application claiming this invention has been filed. The research underlying this invention has been published, in Gunton et al., Cell 122:337–349 (2005).

Type of Offer: Licensing

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