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2022 ◽  
Vol 12 (3) ◽  
pp. 647-652
Yang Zhang ◽  
Peng Sun ◽  
Shuying Han ◽  
Duojiao Fan

Mitochondrial autophagy and inflammatory response involves in diabetes. This study mainly explores the role of Silent Information Regulator (SIRT1) in pancreatic β-cells under high glucose conditions and related mechanism. Pancreatic β cells was cultured in a high-glucose environment with SRT1720 and EX527 respectively to define activation group and inhibition group followed by analysis of SIRT1, P-FOXO1, FOXO1, LC3, ATG5, PINK, Parkin, Mfn1, Mfn2, Fis1, IL-6, TNF-α, NLRP3 protein and mRNA expression by qRT-PCR, Western blot and fluorescent probe technology. Compared with control group, SIRT1 protein and mRNA expression in the high glucose group was significantly reduced. Activation group had highest protein and mRNA expression of SIRT1 P-FOXO1, FOXO1, Mfn1, Mfn2, Fis1, PINK, Parkin and mitochondrial membrane potential followed by blank group and inhibition group.SIRT1 secretion by pancreatic β-cells under high glucose environment is reduced. After activating SIRT1, mitochondrial autophagy decreased significantly and inflammatory response is significantly alleviated, indicating that SIRT1 might be used as a therapeutic target.

Wenxia Ren ◽  
Miaomiao Chai ◽  
Mingli Jiang ◽  
Yan Zhou ◽  
Wensong Tan

2022 ◽  
Vol 12 ◽  
Xuguang Zhang ◽  
Yuxin Zhang ◽  
Mingyan Zhou ◽  
Yiqiang Xie ◽  
Xiujuan Dong ◽  

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 160
Katharina Murillo ◽  
Azat Samigullin ◽  
Per M. Humpert ◽  
Thomas Fleming ◽  
Kübra Özer ◽  

C. elegans are used to study molecular pathways, linking high glucose levels (HG) to diabetic complications. Persistent exposure of C. elegans to a HG environment induces the mitochondrial formation of reactive oxygen species (ROS) and advanced glycation endproducts (AGEs), leading to neuronal damage and decreased lifespan. Studies suggest that transient high glucose exposure (TGE) exerts different effects than persistent exposure. Thus, the effects of TGE on ROS, AGE-formation and life span were studied in C. elegans. Four-day TGE (400 mM) as compared to controls (0mM) showed a persistent increase of ROS (4-days 286 ± 40 RLUs vs. control 187 ± 23 RLUs) without increased formation of AGEs. TGE increased body motility (1-day 0.14 ± 0.02; 4-days 0.15 ± 0.01; 6-days 0.16 ± 0.02 vs. control 0.10 ± 0.02 in mm/s), and bending angle (1-day 17.7 ± 1.55; 3-days 18.7 ± 1.39; 6-days 20.3 ± 0.61 vs. control 15.3 ± 1.63 in degree/s) as signs of neuronal damage. Lifespan was increased by 27% (21 ± 2.4 days) after one-day TGE, 34% (22 ± 1.2 days) after four-days TGE, and 26% (21 ± 1.4 days) after six-days TGE vs. control (16 ± 1.3 days). These experiments suggest that TGE in C. elegans has positive effects on life span and neuronal function, associated with mildly increased ROS-formation. From the perspective of metabolic memory, hormetic effects outweighed the detrimental effects of a HG environment.

2022 ◽  
Vol 8 ◽  
Darukeshwara Joladarashi ◽  
Yanan Zhu ◽  
Matthew Willman ◽  
Kevin Nash ◽  
Maria Cimini ◽  

Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis that leads to progressive heart failure. The mechanisms underlying DCM pathogenesis remain obscure, and no effective treatments for the disease have been available. In the present study, we observed that STK35, a novel kinase, is decreased in the diabetic human heart. High glucose treatment, mimicking hyperglycemia in diabetes, downregulated STK35 expression in mouse cardiac endothelial cells (MCEC). Knockdown of STK35 attenuated MCEC proliferation, migration, and tube formation, whereas STK35 overexpression restored the high glucose-suppressed MCEC migration and tube formation. Angiogenesis gene PCR array analysis revealed that HG downregulated the expression of several angiogenic genes, and this suppression was fully restored by STK35 overexpression. Intravenous injection of AAV9-STK35 viral particles successfully overexpressed STK35 in diabetic mouse hearts, leading to increased vascular density, suppression of fibrosis in the heart, and amelioration of left ventricular function. Altogether, our results suggest that hyperglycemia downregulates endothelial STK35 expression, leading to microvascular dysfunction in diabetic hearts, representing a novel mechanism underlying DCM pathogenesis. Our study also emerges STK35 is a novel gene therapeutic target for preventing and treating DCM.

Energies ◽  
2022 ◽  
Vol 15 (2) ◽  
pp. 561
Koudkeo Phommachan ◽  
Chansom Keo-oudone ◽  
Mochamad Nurcholis ◽  
Nookhao Vongvilaisak ◽  
Mingkhuan Chanhming ◽  

Candida tropicalis, a xylose-fermenting yeast, has the potential for converting cellulosic biomass to ethanol. Thermotolerant C. tropicalis X-17, which was isolated in Laos, was subjected to repetitive long-term cultivation with a gradual increase in temperature (RLCGT) in the presence of a high concentration of glucose, which exposed cells to various stresses in addition to the high concentration of glucose and high temperatures. The resultant adapted strain demonstrated increased tolerance to ethanol, furfural and hydroxymethylfurfural at high temperatures and displayed improvement in fermentation ability at high glucose concentrations and xylose-fermenting ability. Transcriptome analysis revealed the up-regulation of a gene for a glucose transporter of the major facilitator superfamily and genes for stress response and cell wall proteins. Additionally, hydropathy analysis revealed that three genes for putative membrane proteins with multiple membrane-spanning segments were also up-regulated. From these findings, it can be inferred that the up-regulation of genes, including the gene for a glucose transporter, is responsible for the phenotype of the adaptive strain. This study revealed part of the mechanisms of fermentability at high glucose concentrations in C. tropicalis and the results of this study suggest that RLCGT is an effective procedure for improving multistress tolerance.

2022 ◽  
Gabriel Richard ◽  
Denis P. Blondin ◽  
Saad A. Syed ◽  
Laura Rossi ◽  
Michelle E. Fontes ◽  

Diets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with insulin resistance and dyslipidemia during fructose overconsumption in humans.

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