Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

Abstract

Diabetes mellitus (DM) is characterized by the appearance of progressive kidney damage, which may progress to end-stage kidney disease. The control of hyperglycemia is usually not sufficient to halt this progression. The kidney damage is quantitatively and qualitatively different in the two forms of diabetes; the typical nodular fibrosis (Kimmelstiel Wilson nodules) appears mostly in type 1 DM, whereas glomerulomegaly is primarily present in type 2 obese DM. An analysis of the different metabolites and hormones in type 1 and type 2 DM and their differential pharmacological treatments might be helpful to advance the hypotheses on the different histopathological patterns of the kidneys and their responses to sodium/glucose transporter type 2 inhibitors (SGLT2i).

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy

“…A chronic hyperglycemia state is certainly a common feature in type 1 and type 2 diabetes, but the body weights and biochemical characteristics of these two models may have slight differences (Table 1). These differences cannot be explained by hyperglycemia toxicity as there are many mechanisms independent from hyperglycemia involved in the pathogenesis of diabetes [28,29]. We sought to determine the morphological change due to ER stress in the podocytes of the DN mice [12], and the typical ER dilatations were revealed in both the STZ plus UNx and db/db plus UNx groups (Figures 1D and S1C).…”