ADCY3 and diabetes mellitus: To this end, a persistent elevation of PKA activity stemming from diabetes-induced upregulation of both AC3, AC8 and downregulation of PDE3A (M.S.B. and F.A-M., unpublished observation), which are the main controllers of the temporal and spatial features of cellular cAMP production, could, by means of a positive-feedback mechanism, enhance ICER expression and consequently inhibit the transcriptional activity of CRE.