Human Aldose Reductase (AKR1B1) Enzyme

Background

AKR1B1, also known as aldose reductase, is a key enzyme in the polyol pathway that converts glucose to sorbitol under hyperglycemic conditions. It has a significant role in the pathogenesis of diabetic complications, such as neuropathy, nephropathy, and retinopathy, as sorbitol accumulation induces osmotic stress and oxidative damage. AKR1B1 also metabolizes reactive aldehydes, including lipid peroxidation products like 4-hydroxynonenal (4-HNE), contributing to cellular detoxification under oxidative stress. Its overactivation under diabetic and inflammatory conditions exacerbates oxidative stress and inflammatory signaling pathways. AKR1B1 inhibitors have been developed as potential therapeutic agents for managing diabetic complications. Beyond diabetes, AKR1B1 is involved in steroid metabolism and the detoxification of xenobiotics. It has also been implicated in cancer progression, as its expression is upregulated in some tumors, promoting proliferation and chemoresistance by reducing reactive aldehydes and maintaining cellular redox balance.