The invention provides methods of screening for compounds that increase levels or activity of Aryl hydrocarbon Nuclear Receptor Translocator (ARNT) and/or Hypoxia Inducible Factor 1.alpha. (HIF1.alpha.), for the treatment and prevention of diabetes-related disorders, including type 1 and type 2 diabetes mellitus, impaired glucose tolerance, insulin resistance and beta cell dysfunction; compounds identified by said screening methods; and methods of using said compounds. Also included are methods for treating or preventing diabetes-related diseases using ARNT and/or HIF1.alpha. polypeptides and polynucleotides, and for using information regarding the expression, level or activity of ARNT and/or HIF1.alpha. in predictive medicine, e.g., diagnostic assays, prognostic assays, monitoring clinical trials, and pharmacogenetics.