Experimental Approaches to Diabetic Nephropathy: Cellular Models, Inducing Agents, and Pathophysiological Mechanisms

A chronic metabolic disease known as diabetes mellitus (DM) can be caused by either impaired insulin sensitivity or inadequate insulin synthesis. Elevated blood sugar levels are a symptom of this illness, which disrupts the body's normal digestion of proteins, lipids, and carbohydrates. Systemic consequences such as retinopathy, neuropathy, nephropathy, and cardiovascular disease result from chronic hyperglycemia, making diabetes mellitus the main cause of endocrine morbidity worldwide. Nephropathy, or diabetic nephropathy, is a serious microvascular complication of diabetes. It is well-known to contribute significantly to chronic kidney disease and end-stage renal failure. Glucose transporter-1 (GLUT1) upregulation, polyol and hexosamine pathway activation, advanced glycation end product (AGE) accumulation, protein kinase C (PKC) signalling, oxidative stress, and renin-angiotensin system (RAS) activation are all mechanisms that contribute to diabetic nephropathy (DN). When these routes come together, they promote glomerulosclerosis, interstitial fibrosis, and mesangial enlargement. There are large racial and ethnic differences in the risk of diabetic nephropathy, and the prevalence of diabetes is rapidly increasing worldwide, according to epidemiological data, especially in low- and middle-income countries. The molecular underpinnings of diabetic nephropathy (DN) and therapeutic approaches have been greatly elucidated by experimental models, including in vitro β cell lines and in vivo induction using agents such as streptozotocin, alloxan, high-fat diets, and combined HFD-STZ regimens.