scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

scholarly journals The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Lamiaa M. Shawky ◽  
Ahmed A. Morsi ◽  
Eman El Bana ◽  
Safaa Masoud Hanafy
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Dipeptidyl Peptidase 4

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

scholarly journals Wushenziye Formula Inhibits Pancreatic β Cell Apoptosis in Type 2 Diabetes Mellitus via MEK-ERK-Caspase-3 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chunyu Tian ◽  
Hong Chang ◽  
Xiaojin La ◽  
Ji-an Li ◽  
Leilei Ma
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fasting Blood Glucose ◽  
Min6 Cells

Background. Wushenziye formula (WSZYF), composed of Radix Polygoni Multiflori Preparata, Mori fructus, Mori folium, and Cassiae semen, is effective in the treatment of type 2 diabetes mellitus (T2DM). Aim. In this study, we aimed to explore the effects and the underlying mechanisms of WSZYF on inhibiting pancreatic β cell apoptosis and improving insulin resistance (IR) in T2DM. Methods. A T2DM model was induced by Goto-Kakizaki diabetes prone rats. Cell apoptosis model was induced in MIN6 cells. Results. In vivo, WSZYF decreased fasting blood glucose (FBG), insulin concentration, insulin resistance index, triglyceride (TG), total cholesterol (TC), and free fatty acids (FFA) in T2DM rats. Meanwhile, WSZYF ameliorated impairments in the morphology and structure of pancreatic tissues. In vitro, WSZYF enhanced cell viability and promoted insulin secretion in the apoptosis model of MIN6 cells. Furthermore, WSZYF modulated the expressions of apoptosis-related molecules by increasing the expressions of MEK1/2, p-MEK1/2, ERK1/2, and p-ERK1/2 and decreasing the cleaved-caspase-3 expression. Conclusion. These findings indicate that WSZYF may become a new drug candidate in the treatment of T2DM and its antidiabetic mechanism is probably inhibiting pancreatic β cell apoptosis by modulating the MEK-ERK-Caspase-3 signaling pathway.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function

2011 ◽  
Vol 301 (6) ◽  
pp. E1220-E1228 ◽  
Author(s):  
Christine Hamann ◽  
Claudia Goettsch ◽  
Jan Mettelsiefen ◽  
Veit Henkenjohann ◽  
Martina Rauner ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Bone Regeneration ◽  
Rat Model ◽  
Diabetic Rats ◽  
Low Bone Mass ◽  
Insulin Resistant ◽  
Zdf Rats

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (−20%) and mineralized matrix formation (−55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40–80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

scholarly journals The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2 Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through the Upregulation of Glutathione Synthesis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Andréia Quatrin ◽  
Lisiane Conte ◽  
Dariane Trivisiol da Silva ◽  
Cassieli Gehlen Figueiredo ◽  
Sabrina Somacal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Antioxidant Properties ◽  
Redox Balance ◽  
Diabetic Rats ◽  
Hepatic Damage ◽  
Glutathione Synthesis

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzymeδ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

Cinammon (Cinnamomum Spp.) and Type 2 Diabetes Mellitus

2019 ◽  
Vol 18 (3) ◽  
pp. 247-255
Author(s):  
Sierra-Puente D. ◽  
Abadi-Alfie S. ◽  
Arakanchi-Altaled K. ◽  
Bogard-Brondo M. ◽  
García-Lascurain M. ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Key Aspects

Spices such as cinnamon (Cinnamomum Spp.) have been of interest due to their phytochemical composition that exert hypoglycemic effects with potential for management of type 2 diabetes mellitus (T2DM). We summarize data from 27 manuscripts that include, one book chapter, 3 review articles, 10 randomized controlled trials, 4 systematic reviews with meta-analysis, and 9 preclinical studies. The most frequently used cinnamon variety was Cinnamomum cassia rather than the Cinnamomum zeylanicum, whereas outcomes were defined as fasting blood glucose, glycated hemoglobin, and oral glucose tolerance test. A great variability in methodology such as different doses (from 120 mg to 6 g), duration of intervention, data retrieved and use of different concomitant medication, were found to be key aspects of most of trials and systematic reviews with meta-analysis available to date. Low quality studies have been made in most cases with a lot of heterogeneity clouding significance of results. More research needs to be done in order to yield accurate evidence for evidence-based recommendations. Its use is not currently a reliable nor advisable option for the treatment of T2DM.

Epigenetic modulation of autophagy genes linked to diabetic nephropathy by administration of isorhamnetin in Type 2 diabetes mellitus rats

Epigenomics ◽  
2021 ◽  
Author(s):  
Marwa Matboli ◽  
Doaa Ibrahim ◽  
Amany H Hasanin ◽  
Mohamed Kamel Hassan ◽  
Eman K Habib ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Light And Electron Microscopy ◽  
Lipid Profiles ◽  
Mirna Regulation ◽  
Protein Levels

Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes ( FYCO1, ULK, TECPR1 and  WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.

scholarly journals Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

2020 ◽  
Vol 17 (16) ◽  
pp. 5866
Author(s):  
Zarish Noreen ◽  
Christopher A. Loffredo ◽  
Attya Bhatti ◽  
Jyothirmai J. Simhadri ◽  
Gail Nunlee-Bland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Health Concern ◽  
Receptor Signaling ◽  
Small Pilot Study

The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6, TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling, Type II Diabetes Mellitus Signaling, Apoptosis Signaling, Aryl Hydrocarbon Receptor Signaling, p53 Signaling, Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling, Parkinson’s Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway, Oxidative Phosphorylation, LXR/RXR Activation, and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.

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