Icariin ameliorates streptozocin-induced diabetic nephropathy through suppressing the TLR4/NF-κB signal pathway

2021 ◽  
Vol 12 (3) ◽  
pp. 1241-1251
Author(s):  
Min-you Qi ◽  
Ying-hao He ◽  
Yin Cheng ◽  
Qing Fang ◽  
Ru-yu Ma ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signal Pathway ◽  
Protective Effects ◽  
Diabetic Mice

Protective effects of icariin on streptozotocin-induced diabetic mice by inhibiting the TLR4/NF-κB signal pathway.

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

Protective effects of a mitochondria-targeted small peptide SS31 against hyperglycemia-induced mitochondrial abnormalities in the liver tissues of diabetic mice, Tallyho/JngJ mice

Mitochondrion ◽  
2021 ◽  
Vol 58 ◽  
pp. 49-58 ◽  
Author(s):  
Jasvinder Singh Bhatti ◽  
Kavya Tamarai ◽  
Ramesh Kandimalla ◽  
Maria Manczak ◽  
Xiangling Yin ◽  
...  
Keyword(s):  
Protective Effects ◽  
Diabetic Mice ◽  
Small Peptide ◽  
Mitochondrial Abnormalities ◽  
Liver Tissues

scholarly journals Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jayarami Reddy Medapati ◽  
Deepthi Rapaka ◽  
Veera Raghavulu Bitra ◽  
Santhosh Kumar Ranajit ◽  
Girija Sankar Guntuku ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Morphological Changes ◽  
Serum Levels ◽  
Cb1 Receptors ◽  
Protective Effects ◽  
Renal Hypertrophy ◽  
Necrosis Factor Alpha

Abstract Background The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Results The progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001). Conclusions From the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy. Graphical abstract

scholarly journals Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1379
Author(s):  
Dongjoon Kim ◽  
Hiromi Sesaki ◽  
Sayon Roy
Keyword(s):  
Diabetic Retinopathy ◽  
Cell Loss ◽  
Vascular Lesions ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Wild Type ◽  
Apoptotic Genes ◽  
Retinal Vascular Lesions ◽  
Acellular Capillaries ◽  
Pericyte Loss

High glucose (HG)-induced Drp1 overexpression contributes to mitochondrial dysfunction and promotes apoptosis in retinal endothelial cells. However, it is unknown whether inhibiting Drp1 overexpression protects against the development of retinal vascular cell loss in diabetes. To investigate whether reduced Drp1 level is protective against diabetes-induced retinal vascular lesions, four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Drp1+/− mice, and STZ-induced diabetic Drp1+/− mice were examined after 16 weeks of diabetes. Western Blot analysis indicated a significant increase in Drp1 expression in the diabetic retinas compared to those of WT mice; retinas of diabetic Drp1+/− mice showed reduced Drp1 level compared to those of diabetic mice. A significant increase in the number of acellular capillaries (AC) and pericyte loss (PL) was observed in the retinas of diabetic mice compared to those of the WT control mice. Importantly, a significant decrease in the number of AC and PL was observed in retinas of diabetic Drp1+/− mice compared to those of diabetic mice concomitant with increased expression of pro-apoptotic genes, Bax, cleaved PARP, and increased cleaved caspase-3 activity. Preventing diabetes-induced Drp1 overexpression may have protective effects against the development of vascular lesions, characteristic of diabetic retinopathy.

scholarly journals Low-Dose Radiation Activates Akt and Nrf2 in the Kidney of Diabetic Mice: A Potential Mechanism to Prevent Diabetic Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao Xing ◽  
Chi Zhang ◽  
Minglong Shao ◽  
Qingyue Tong ◽  
Guirong Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Low Dose ◽  
X Rays ◽  
Diabetic Mice ◽  
Low Dose Radiation ◽  
Single Exposure ◽  
Akt Phosphorylation ◽  
And Function ◽  
Nrf2 Expression ◽  
Dose Radiation

Repetitive exposure of diabetic mice to low-dose radiation (LDR) at 25 mGy could significantly attenuate diabetes-induced renal inflammation, oxidative damage, remodeling, and dysfunction, for which, however, the underlying mechanism remained unknown. The present study explored the effects of LDR on the expression and function of Akt and Nrf2 in the kidney of diabetic mice. C57BL/6J mice were used to induce type 1 diabetes with multiple low-dose streptozotocin. Diabetic and age-matched control mice were irradiated with whole body X-rays at either single 25 mGy and 75 mGy or accumulated 75 mGy (25 mGy daily for 3 days) and then sacrificed at 1–12 h for examining renal Akt phosphorylation and Nrf2 expression and function. We found that 75 mGy of X-rays can stimulate Akt signaling pathway and upregulate Nrf2 expression and function in diabetic kidneys; single exposure of 25 mGy did not, but three exposures to 25 mGy of X-rays could offer a similar effect as single exposure to 75 mGy on the stimulation of Akt phosphorylation and the upregulation of Nrf2 expression and transcription function. These results suggest that single 75 mGy or multiple 25 mGy of X-rays can stimulate Akt phosphorylation and upregulate Nrf2 expression and function, which may explain the prevention of LDR against the diabetic nephropathy mentioned above.

scholarly journals Induction of leukocyte adhesion molecules and renal physiologically active molecules in Porphyromonas gingivalis lipopolysaccharide-induced diabetic nephropathy

2020 ◽  
Author(s):  
Koichiro Kajiwara ◽  
Yoshihiko Sawa ◽  
Takahiro Fujita ◽  
Sachio Tamaoki
Keyword(s):  
Diabetic Nephropathy ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Diabetic Mouse ◽  
Renal Parenchyma ◽  
Periodontal Pathogen ◽  
Diabetic Patients ◽  
Renal Tubules ◽  
Diabetic Mice ◽  
Leukocyte Adhesion Molecules

Abstract Background We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and established that the TLR2 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (LPS) induces nephropathy in diabetic mice. It is thought that P. gingivalis LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of P. gingivalis LPS via TLR in the diabetic kidneys. The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in mouse kidneys with periodontal pathogen P. gingivalis LPS-induced diabetic nephropathy that was recently established. Methods The immunohistochemical investigation was performed on mouse kidney with P. gingivalis LPS-induced diabetic nephropathy model with glomerulosclerosis in glomeruli. Results There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in diabetic mice, or in healthy mice administered P. gingivalis LPS. However, in diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy the expression of VCAM-1 and the accumulation of FGF23 were established in renal tubules and glomeruli, and the expression of E-selectin was established in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions including not in distal tubules of diabetic mice without LPS, and not in healthy mice administered P. gingivalis LPS. In diabetic mouse kidneys with P. gingivalis LPS-induced nephropathy ACE2 was detected both in renal tubules as well as in glomeruli. The macrophage-1 (Mac-1) and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was accumulation in P. gingivalis LPS-induced diabetic nephropathy. As the expression of VCAM-1 and E-selectin is upregulated in glomeruli, tubules, and intertubular capillaries, it is thought that the inflammatory infiltration of the monocyte-macrophage lineage promoted in kidneys with P. gingivalis LPS-induced the diabetic nephropathy. Conclusions P. gingivalis LPS may progressively accelerate the development of the renal inflammatory environment in LPS-accumulated glomeruli with the macrophage infiltration via the renal expression of VCAM-1 and E-selectin, and with ACE2 overexpression and FGF23 accumulation. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.

scholarly journals High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

2016 ◽  
Vol 113 (8) ◽  
pp. 2218-2222 ◽  
Author(s):  
Catherine K. Hathaway ◽  
Albert S. Chang ◽  
Ruriko Grant ◽  
Hyung-Suk Kim ◽  
Victoria J. Madden ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Association Studies ◽  
Lipid Peroxides ◽  
Transforming Growth Factor Β1 ◽  
Genome Wide Association Studies ◽  
Diabetic Mice ◽  
Stage Renal Disease ◽  
End Stage

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2Akita gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

Sign in / Sign up

Export Citation Format

Share Document