Conversely, MDM2, an E3 ubiquitin ligase that modulates JAK–STAT and PI3K–Akt signaling and plays a protective role in diabetic kidney disease through NRF-2 regulation [89–92], was significantly downregulated in diabetic dogs, with no observed improvement detected after astaxanthin supplementation. The gene discussed is AKT1; the disease is diabetic kidney disease.