Recovery of Diabetic Rats After Physical Exhaustion: Kinetic Alterations in Muscle Inflammation and Muscle-Signaling Proteins to Atrophy and Hypertrophy

Despite the updated knowledge of the impact of gut dysbiosis on diabetes, investigations into the beneficial effects of individual bacteria are still required. This study evaluates the antihyperglycemic efficacy of Lactobacillus paracasei HII01 and its possible mechanisms in diabetic rats. Diabetic rats were assigned to receive vehicle, L. paracasei HII01 (108 CFU/day), metformin 30 (mg/kg) or a combination of L. paracasei HII01 and metformin. Normal rats given vehicle and L. paracasei HII01 were included. Metabolic parameters, including in vitro hemi-diaphragm glucose uptake, skeletal insulin-signaling proteins, plasma lipopolysaccharide (LPS), gut permeability, composition of gut microbiota and its metabolites, as well as short-chain fatty acids (SCFAs), were assessed after 12 weeks of experiment. The results clearly demonstrated that L. paracasei HII01 improved glycemic parameters, glucose uptake, insulin-signaling proteins including pAktSer473, glucose transporter 4 (GLUT4) and phosphorylation of AMP-activated protein kinase (pAMPKThr172), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-kB) in diabetic rats. Modulation of gut microbiota was found together with improvement in leaky gut, endotoxemia and SCFAs in diabetic rats administered L. paracasei HII01. In conclusion, L. paracasei HII01 alleviated hyperglycemia in diabetic rats primarily by modulating gut microbiota along with lessening leaky gut, leading to improvement in endotoxemia and inflammation-disturbed insulin signaling, which was mediated partly by PI3K/Akt signaling and AMPK activation.

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Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/β-catenin signaling

AJP Renal Physiology ◽

10.1152/ajprenal.00128.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. F458-F468 ◽

Cited By ~ 3

Author(s):

Linjing Huang ◽

Tingting Lin ◽

Meizhen Shi ◽

Xiuqing Chen ◽

Peiwen Wu

Keyword(s):

Diabetic Nephropathy ◽

Collagen Type ◽

Mesangial Cells ◽

Smooth Muscle Actin ◽

Diabetic Rats ◽

Collagen Type Iv ◽

Signaling Proteins ◽

Muscle Actin ◽

Type Iv

The Wnt/β-catenin signaling pathway is involved in production of the extracellular matrix (ECM) by mesangial cells (MCs). Recent studies by us and others have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have protective effects against diabetic nephropathy. The purpose of the present study was to investigate whether the Wnt/β-catenin signaling in MCs contributes to GLP-1RA-induced inhibition of ECM accumulation and mitigation of glomerular injury in diabetic nephropathy. In cultured human mesangial cells, liraglutide (a GLP-1RA) treatment significantly reduced high glucose (HG)-stimulated production of fibronectin, collagen type IV, and α-smooth muscle actin, and the liraglutide effects were significantly attenuated by XAV-939, a selective inhibitor of Wnt/β-catenin signaling. Furthermore, HG treatment significantly decreased protein abundance of Wnt4, Wnt5a, phospho-glycogen synthase kinase-3β, and β-catenin. These HG effects on Wnt/β-catenin signaling proteins were significantly blunted by liraglutide treatment. For in vivo experiments, we administered liraglutide (200 μg·kg−1·12 h−1) by subcutaneous injection to streptozocin-induced type 1 diabetic rats for 8 wk. Administration of liraglutide significantly improved elevated blood urine nitrogen, serum creatinine, and urinary albumin excretion rate and alleviated renal hypertrophy, mesangial expansion, and glomerular fibrosis in type 1 diabetic rats, whereas blood glucose level and body weight did not have significant changes. Consistent with the in vitro experiments, liraglutide treatment significantly reduced the diabetes-induced increases in glomerular fibronectin, collagen type IV, and α-smooth muscle actin and decreases in glomerular Wnt/β-catenin signaling proteins. These results suggest that liraglutide alleviated glomerular ECM accumulation and renal injury in diabetic nephropathy by enhancing Wnt/β-catenin signaling.

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The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic non-obese type 2 diabetic rats: A differential role of unfolded protein response (UPR) signaling proteins

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2012.09.017 ◽

2013 ◽

Vol 45 (2) ◽

pp. 438-447 ◽

Cited By ~ 51

Author(s):

Arun Prasath Lakshmanan ◽

Meilei Harima ◽

Kenji Suzuki ◽

Vivian Soetikno ◽

Masaki Nagata ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Diabetic Cardiomyopathy ◽

Diabetic Rats ◽

Signaling Proteins ◽

Unfolded Protein ◽

Protein Response ◽

Type 2 Diabetic

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High glucose and diabetes enhanced store-operated Ca2+ entry and increased expression of its signaling proteins in mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00463.2013 ◽

2014 ◽

Vol 306 (9) ◽

pp. F1069-F1080 ◽

Cited By ~ 34

Author(s):

Sarika Chaudhari ◽

Peiwen Wu ◽

Yanxia Wang ◽

Yanfeng Ding ◽

Joseph Yuan ◽

...

Keyword(s):

High Glucose ◽

Mesangial Cells ◽

Cyclopiazonic Acid ◽

Diabetic Rats ◽

Type I ◽

Signaling Proteins ◽

Glomerular Mesangial Cells ◽

Rt Pcr ◽

Protein Expressions ◽

Normal Glucose

The present study was conducted to determine whether and how store-operated Ca2+ entry (SOCE) in glomerular mesangial cells (MCs) was altered by high glucose (HG) and diabetes. Human MCs were treated with either normal glucose or HG for different time periods. Cyclopiazonic acid-induced SOCE was significantly greater in the MCs with 7-day HG treatment and the response was completely abolished by GSK-7975A, a selective inhibitor of store-operated Ca2+ channels. Similarly, the inositol 1,4,5-trisphosphate-induced store-operated Ca2+ currents were significantly enhanced in the MCs treated with HG for 7 days, and the enhanced response was abolished by both GSK-7975A and La3+. In contrast, receptor-operated Ca2+ entry in MCs was significantly reduced by HG treatment. Western blotting showed that HG increased the expression levels of STIM1 and Orai1 in cultured MCs. A significant HG effect occurred at a concentration as low as 10 mM, but required a minimum of 7 days. The HG effect in cultured MCs was recapitulated in renal glomeruli/cortex of both type I and II diabetic rats. Furthermore, quantitative real-time RT-PCR revealed that a 6-day HG treatment significantly increased the mRNA expression level of STIM1. However, the expressions of STIM2 and Orai1 transcripts were not affected by HG. Taken together, these results suggest that HG/diabetes enhanced SOCE in MCs by increasing STIM1/Orai1 protein expressions. HG upregulates STIM1 by promoting its transcription but increases Orai1 protein through a posttranscriptional mechanism.

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Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

PLoS ONE ◽

10.1371/journal.pone.0172429 ◽

2017 ◽

Vol 12 (5) ◽

pp. e0172429 ◽

Cited By ~ 15

Author(s):

Mahmoud Balbaa ◽

Shaymaa A. Abdulmalek ◽

Sofia Khalil

Keyword(s):

Oxidative Stress ◽

Insulin Signaling ◽

Nigella Sativa ◽

Diabetic Rats ◽

Antidiabetic Drugs ◽

Signaling Proteins ◽

Nigella Sativa Oil ◽

The Brain

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Sites of Insulin Action Using Ferritin Labeling

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066759 ◽

1971 ◽

Vol 29 ◽

pp. 540-541

Author(s):

Burton B. Silver ◽

Ronald S. Nelson

Keyword(s):

Electron Microscopy ◽

Binding Sites ◽

Anterior Pituitary ◽

Insulin Action ◽

Diabetic Rats ◽

Insulin Antibody ◽

Fat Pad ◽

Target Organs ◽

Uranium Salts ◽

Sugar Levels

Some investigators feel that insulin does not enter cells but exerts its influence in some manner on the cell surface. Ferritin labeling of insulin and insulin antibody was used to determine if binding sites of insulin to specific target organs could be seen with electron microscopy.Alloxanized rats were considered diabetic if blood sugar levels were in excess of 300 mg %. Test reagents included ferritin, ferritin labeled insulin, and ferritin labeled insulin antibody. Target organs examined were were diaphragm, kidney, gastrocnemius, fat pad, liver and anterior pituitary. Reagents were administered through the left common carotid. Survival time was at least one hour in test animals. Tissue incubation studies were also done in normal as well as diabetic rats. Specimens were fixed in gluteraldehyde and osmium followed by staining with lead and uranium salts. Some tissues were not stained.

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