CUBN and diabetic kidney disease: In contrast to DKD, we named this kind of renal structural damage and functional changes as “IGT kidney disease.” By inhibiting the IRS-1/PI3-K/Akt signaling pathway, high concentration of insulin downregulates the expression of megalin and cubilin, which then causes the reabsorption dysfunction of albumin by renal tubular epithelial cells leading to albuminuria.