CLOCK and diabetes mellitus: Hyperglycemia was shown to decrease the expression level of the negative clock arm genes, per 1 and per 2 in cultured Rat-1 fibroblasts [35], per1 and per2 gene expression was downregulated in the liver [36], [37] and kidney [38] of diabetic mice, and the degree of downregulation was dependent on the severity of diabetes [39].