KL and diabetes mellitus: Furthermore, a few studies have evaluated the therapeutic effects of recombinant Klotho and the stimulation of Klotho overexpression (e.g., by calcitriol, peroxisome proliferator-activated receptor γ [41], substances like pioglitazone [7] and Klotho gene delivery through a viral vector), which downregulated oxidative stress, ameliorated the high glucose-induced injury of renal glomerular endothelial cells in a model of diabetic nephropathy, suppressed diabetes-induced renal hypertrophy, and exerted other immunotherapeutic effects in diabetic nephropathy [12,16,44,59].