From our present culture experiments with glibenclamide or high glucose with a confocal image of high iNOS protein expression and fluorescence intensity as well as a subsequent reduction of the insulin secretory capacity following a glucose challenge, it seems conceivable to assume that β-cell failure after long term hyperglycemia as well as after long term monotherapy with glibenclamide is, at a considerable part, due to the induction of iNOS and a long-time overproduction of iNOS-derived NO in the beta-cells. This evidence concerns the gene NOS2 and Hyperglycemia.