Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes

Abstract

PURPOSE:To investigate in the kidney the pathologic changes and expression of GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and streptozotocin-induced diabetes. METHODS:Sixty two male KM mice were randomly divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were injected intraperitoneally with streptozotocin to induce diabetes. After diabetic models were successfully established, the kidneys were excised and conserved for further test. RESULTS:No significant difference in the body weight was observed after the dietary manipulation (p=0.554). After the streptozotocin was injected, fasting blood glucose levels in the diabetes group (DM) were significantly higher than that in the NC group (p<0.0001).Glomerular atrophy observed under light microscope in the DM group was more serious compared with the NC group. The expression of GRP78 and CHOP in the kidneys of the mice in the DM group were higher compared with the NC group. CONCLUSION:Renal lesion occurs in the diabetic Kunming mice induced by combination of high-fat diet and low-dose streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the injury process.

Inhibition of endoplasmic reticulum stress prevents high‐fat diet mediated atrial fibrosis and fibrillation

“…15 High-fat diet and streptozotocin-induced diabetes could lead to the renal lesion, and endoplasmic reticulum stress and CHOP may contribute to the injury process. 16 Despite numerous clues of ERS in HFD-induced inflammation and stress, there was minimal evidence of the role of ERS in AF. To assess the role of ERS in obesity and AF, we tested the ERS activity in overweight patients and controls, which demonstrated that the ERS process was activated in atrial myocardium of obese patients, in line with previous reports.…”

“…Another study demonstrated that targeting ERS could ameliorate retinal inflammation caused by HFD 15 . High‐fat diet and streptozotocin‐induced diabetes could lead to the renal lesion, and endoplasmic reticulum stress and CHOP may contribute to the injury process 16 . Despite numerous clues of ERS in HFD‐induced inflammation and stress, there was minimal evidence of the role of ERS in AF.…”

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

“…The endoplasmic reticulum (ER) plays a critical role in protein folding, lipid synthesis, and calcium storage and release (1). Acute nutrient excess or obesity leads to the development of ER stress, triggering the activation of a group of signaling pathways, termed the unfolded protein response (UPR), in the liver, kidneys (2), and other organs. Three ER-stress-activated enzymesinositol-requiring enzyme 1 (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6)together maintain ER homeostasis by activating distinct branches of the UPR.…”