The present study reveals that in the retina of individuals with diabetes, PKC and p38α MAPK are continually activated by hyperglycemia, leading to an upregulation of Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase that was once unidentified as a target of PKC signaling. This evidence concerns the gene PRRT2 and diabetes mellitus.