scholarly journals Effect of Gegen Qinlian Decoction on Hepatic Gluconeogenesis in ZDF Rats with Type 2 Diabetes Mellitus Based on the Farnesol X Receptor/Ceramide Signaling Pathway Regulating Mitochondrial Metabolism and Endoplasmic Reticulum Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qi Zhou ◽  
Ning Song ◽  
Shi-qi Wang ◽  
Yan Wang ◽  
Yi-kun Zhao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Blood Glucose ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Liver Mitochondria ◽  
Hepatic Gluconeogenesis ◽  
Acetyl Coa ◽  
Expression Levels

Background. Type 2 diabetes mellitus (T2DM) is a kind of disorder of glucose and lipid metabolism with the main clinical manifestation of long‐term higher blood glucose level than the normal value. Farnesol X receptor (FXR)/ceramide signaling pathway plays an important role in regulating cholesterol metabolism, lipid homeostasis, and the absorption of fat and vitamins in diet. Gegen Qinlian Decoction (GQD) is a classical herbal formula, which has a good clinical therapeutic effect on diabetes-related metabolic syndrome. Objective. To investigate the effect of Gegen Qinlian Decoction (GQD) on hepatic gluconeogenesis in obese T2DM rats based on the FXR/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress (ERS). Methods. ZDF (fa/fa) rats were fed with high-fat diet to establish the T2DM model; GQD was given to T2DM model rats by gavage; changes of the general state and body weight of rats were recorded; fasting blood glucose was detected; blood insulin, blood ceramide, glycosylated hemoglobin in blood, acetyl CoA in liver mitochondria, and bile salt lyase in intestinal tissue were detected by ELISA. The content of T-β-MCA in blood was detected by LC-MS; the content of glycogen in liver tissue was detected by PAS staining; the expression of FXR, Sptlc2, and Smpd3 in ileum tissue, P-PERK, ATF6α, GRP78 BIP, and P-IRE1 in the liver, and CS and PC protein in liver mitochondria was detected by immunohistochemistry and western blot assay. The mRNA expression levels of FXR, Sptlc2, and Smpd3 in the ileum, PERK, ATF6α, GRP78 BIP, and IRE1 in the liver, and CS and PC in liver mitochondria were detected by qRT-PCR. Results. GQD can improve the general state of T2DM rats, slow down their weight gain, reduce the levels of fasting blood glucose, fasting insulin, glycosylated hemoglobin, blood ceramide, bile salt hydrolase in intestinal tissue, and acetyl CoA in liver mitochondria of T2DM rats, and increase the contents of liver glycogen and T-β-MCA in blood of T2DM rats. At the molecular level, GQD can inhibit the expression levels of FXR, Sptlc2, and Smpd3 in the ileum of T2DM rats and the protein and mRNA expression levels of oxidative stress-related factors in the liver. At the same time, GQD can increase the expression of CS and reduce the expression of PC in liver mitochondria of T2DM rats. Conclusion. GQD can inhibit the FXR/ceramide signaling pathway, regulate endoplasmic reticulum stress, enhance the CS activity of liver mitochondria, reduce the acetyl CoA level and PC activity of liver mitochondria, inhibit hepatic gluconeogenesis, protect islet β-cells, and control blood glucose.

GSK-3β inhibition confers cardioprotection associated with the restoration of mitochondrial function and suppression of endoplasmic reticulum stress in sevoflurane preconditioned rats following ischemia/reperfusion injury

Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 679-686 ◽  
Author(s):  
Yujia Wang ◽  
Chunlin Ge ◽  
Junfeng Chen ◽  
Kun Tang ◽  
Jianjun Liu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Expression Levels ◽  
Sevoflurane Preconditioning ◽  
Gsk 3Β

Background: Sevoflurane has been shown to protect against myocardial ischemia/reperfusion (I/R) injury in animals, while its cardioprotection is lost if the ischemic insult is too long. In this study, we proposed a prevailing hypothesis that GSK-3β inhibitor-mediated activation of GSK-3β/β-catenin signaling pathway provides additional cardioprotection in sevoflurane preconditioned rats following I/R injury. Methods: Rats were subjected to treatment with TDZD-8, a GSK-3β inhibitor, 5 minutes prior to sevoflurane preconditioning and 30-minute ischemia and 120-minute reperfusion. Furthermore, in order to find out whether this cardioprotection is linked with mitochondrial function and endoplasmic reticulum stress (ERS), we isolated mitochondria from rat hearts perfused with TDZD-8 and determined the alternations of ERS markers. Results: Sevoflurane preconditioning or GSK-3β inhibitor treatment prevented cardiomyocyte apoptosis, phosphorylated GSK-3β and accelerated total β-catenin expression levels, reduced mitochondrial permeability transition pore (MPTP) activity, promoted the recovery of mitochondrial membrane potential and decreased the expression levels of GRP78, caspase-12 and C/EBP homology protein (CHOP) in rats under I/R condition, suggesting sevoflurane preconditioning or TDZD-8 activate the GSK-3β/β-catenin signaling pathway, improve mitochondria function and suppress ERS occurrence. Conclusions: Taken together, the findings obtained from the study support the concept that sevoflurane preconditioning confers cardioprotection against myocardial I/R injury and GSK-3β/β-catenin signaling activation mediated by TDZD-8 as a novel target to prolong cardioprotection by sevoflurane anaesthesia.

scholarly journals Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yang Chen ◽  
Fuping Zhang ◽  
Di Wang ◽  
Lan Li ◽  
Haibo Si ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Mesenchymal Stem Cells ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Stress Responses ◽  
Lung Fibrosis ◽  
Expression Levels

Diabetes affects a variety of organs such as the kidneys, eyes, and liver, and there is increasing evidence that the lung is also one of the target organs of diabetes and imbalance of Sirt3-mediated stress responses such as inflammation, oxidative stress, apoptosis, autophagy, and ER stress may contribute to diabetic lung fibrosis. Although previous studies have reported that mesenchymal stem cells (MSCs) have beneficial effects on various diabetic complications, the effect and mechanisms of MSCs on diabetes-induced lung injury are not clear. In this study, the STZ-induced diabetes model was constructed in rats, and the effect and potential mechanisms of bone marrow MSCs on diabetic lung fibrosis were investigated. The results revealed that fibrotic changes in the lung were successfully induced in the diabetic rats, while MSCs significantly inhibited or even reversed the changes. Specifically, MSCs upregulated the expression levels of Sirt3 and SOD2 and then activated the Nrf2/ARE signaling pathway, thereby controlling MDA, GSH content, and iNOS and NADPH oxidase subunit p22phox expression levels in the lung tissue. Meanwhile, high levels of Sirt3 and SOD2 induced by MSCs reduced the expression levels of IL-1β, TNF-α, ICAM-1, and MMP9 by suppressing the NF-κB/HMGB1/NLRP3/caspase-1 signaling pathway, as well as regulating the expression levels of cleaved caspasese-3, Bax, and Bcl2 by upregulating the expression level of P-Akt, thereby inhibiting the apoptosis of the lung tissue. In addition, MSCs also regulated the expression levels of LC3, P62, BiP, Chop, and PERK, thereby enhancing autophagy and attenuating endoplasmic reticulum stress. Taken together, our results suggest that MSCs effectively attenuate diabetic lung fibrosis via adjusting Sirt3-mediated responses, including inflammation, oxidative stress, apoptosis, autophagy, and endoplasmic reticulum stress, providing a theoretical foundation for further exploration of MSC-based diabetic therapeutics.

Mycoplasmas bovis P48 induces apoptosis in EBL cells via an endoplasmic reticulum stress-dependent signaling pathway

2021 ◽  
Vol 255 ◽  
pp. 109013
Author(s):  
Xiaochun Wu ◽  
Shengying Zhang ◽  
Cuiqin Long ◽  
Zhen An ◽  
Xiaoyong Xing ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Stress Dependent ◽  
Dependent Signaling Pathway

scholarly journals Effects of Marine Drug Propylene Glycol Alginate Sodium Sulfate on Glucose and Lipid Metabolism in Mice

2021 ◽  
Vol 58 (2) ◽  
pp. 150-154
Author(s):  
Haiyue Liang ◽  
Qun Liu ◽  
Yonghong Xiu
Keyword(s):  
Lipid Metabolism ◽  
Blood Glucose ◽  
Sodium Sulfate ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Control Group ◽  
Distilled Water ◽  
Glucose And Lipid Metabolism ◽  
Propylene Glycol Alginate

Previous studies have shown that marine drug propylene glycol alginate sodium sulfate (PSS) plays important roles in human diseases. This study mainly explored the effects of PSS on hyperglycemia and hyperlipidemia in diabetic db/db mouse models. The db/db mice were randomly divided into 5 groups (n=12), which were model control group (distilled water), positive control group (metformin), PSS low, medium, and high dose groups (PSS25, PSS50, PSS100) and normal control group (C57/BL, distilled water). The mice in each group had free diet and water for 90 days. During the experiment, food intake was recorded every day and body weight was recorded weekly. In addition, fasting blood glucose and glycosylated hemoglobin levels were measured regularly. Finally, the contents of triglyceride (TG), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c) and total cholesterol (TC) in the serum of mice were determined. PSS can significantly reduce fasting blood glucose and glycosylated hemoglobin levels in db/db mice, and improve insulin sensitivity. Moreover, PSS can reduce the fat accumulation of db/db mice and significantly improve the blood lipid level of db/db mice. PSS can significantly improve the symptoms of glucose and lipid metabolism disorders in db/db mice.

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