To explore how diabetes triggers reciprocal regulation of Akt1 and Akt2 in RPE, we investigated the upstream regulators of Akt and found that diabetes increased the ratio of p-PDK1/PDK1 and the ratio of p-PI3K/PI3K in RPE of 2 months diabetic mice compared with age-matched nondiabetic wild type controls. Here, PDK1 is linked to diabetes mellitus.