INS and Hyperglycemia: As hyperglycaemia per se has been reported to downregulate insulin expression as well as stimulate beta cell apoptosis (Olson et al, 1993; Poitout & Robertson, 2002, 2008; Robertson et al, 2004), we used two strategies to circumvent these effects of hyperglycaemia in the TAM-treated Glis3fl/fl/Pdx1CreERT+ mice.