ARNT2: a Novel Target for Diabetes

Description: The invention is based on the discovery of new targets 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, and beta-cell specific knockout mice lacking the ARNT gene developed beta cell dysfunction and diabetes. Because ARNT is known to act as a heterodimer, the inventors then investigated the role of potential partners for ARNT, and discovered that the transcription factor ARNT2 (homologous to ARNT but expressed from a different gene) also has an effect, but an opposite one, on glucose metabolism. Knocking down ARNT2 expression using RNAi resulted in significantly increased glucose stimulated insulin secretion, and decreased ARNT2 expression was accompanied by increased expression of genes known to be involved in glucose metabolism. It therefore appears that inhibition of ARNT2 would be desirable to alleviate the symptoms of diabetes, while enhancement of ARNT function would be desirable for the same purpose. Clinical & Commercial Utility: These inventions provide novel targets 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; while agents that inhibit ARNT2 might also be used for the same purpose. The invention includes methods of drug screening against these targets, to identify potential therapeutic compounds.
U.S. patent applications claiming these inventions have been filed.

Type of Offer: Licensing

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