The Expression of Liver Metabolic Enzymes AMPKα1, AMPKα2, and PGC-1α due to Exercise in Type-2 Diabetes Mellitus Rat Model

BACKGROUND: AMP-activated protein kinase (AMPK) and PGC-1α were crucial metabolism enzymes not only in the skeletal muscles but also in the liver. Exercise can modify metabolic enzymes to improve insulin resistance. AIM: The aim of this study was to analyze the expression of mRNA liver metabolic enzymes gene, that is, AMPKα1, AMPKα2, and PGC-1α in different types and intensities of exercise. METHODS: Healthy male Wistar rats aged 8 weeks in 150–180 g body weight were given a combination of high fat diet for five weeks and low doses of streptozotocin (30 mg/kgbw and 45 mg/kgbw in 0.1 citrate buffer pH 4,5) to develop type 2 diabetes mellitus (T2DM) rat model. Animals then were divided into five groups: One group was sedentary, and four groups were forced to run on the treadmill 3 times/week, 30 min each season, for 8 weeks. mRNA gene expression of AMPKα1, AMPKα2, and PGC-1α was determined with real-time PCR. RESULTS: The results showed that expression of mRNA AMPKα1 in treatment groups was elevated than control and the much expression was showed in continuous types. The expression of mRNA AMPKα2 and PGC-1 α was declined in treatment group which little expression was showed in high intensity for AMPKα2 and moderate intensity for PGC-1 α. Base on type and exercise intensity, mRNA AMPKα1 gene expression much in moderate continuous, mRNA AMPKα2 gene expression higher in high intensity, both continuous and interval training, whereas mRNA PGC-1α gene expression higher in interval groups. CONCLUSION: Various types of aerobic exercises with moderate-vigorous intensities gave different impact to mRNA liver metabolic enzyme genes.

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The Pattern of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Gene Expression in Type-2 Diabetes Mellitus Rat Model Liver: Focus on Exercise

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.6362 ◽

2021 ◽

Vol 9 (T3) ◽

pp. 124-128

Author(s):

Yetty Machrina ◽

Dharma Lindarto ◽

Yunita Sari Pane ◽

Novita Sari Harahap

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

Moderate Intensity ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Treatment Groups

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has an important role in mitochondria biogenesis which generated cellular metabolism. Carbohydrate metabolism in the liver is crucial to maintain plasma blood glucose. AIM: This research aimed to determine the expression of PGC-1α gene in the liver type-2 diabetes mellitus (T2DM) rat model, after treatment with a focus on exercise. METHODS: We used 25 healthy male Wistar rats as subjects. Rats were modified to T2DM models by feeding a high-fat diet and low-dose streptozotocin injection. We divided the rats into five groups, that is, sedentary group as a control and four others as treatment groups. The exercise was assigned for treatment groups by a run on the treadmill as moderate intensity continuous (MIC), highintensity continuous (HIC), slow interval (SI), and fast interval (FI). The treatment groups were exercise throughout 8 weeks with a frequency of 3 times a week. RESULTS: The results showed that expression of PGC-1α gene was lower in all treatment groups compared to controls (p < 0.05). Expression in HIC was higher than MIC (p < 0.05), so was the expression in FI more than SI (p < 0.05). CONCLUSIONS: Exercise affected PGC-1α gene expression in the liver of the T2DM rat model. The expression of PGC-1α was linear with exercise intensity.

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

Journal of International Medical Research ◽

10.1177/0300060521997590 ◽

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.

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Effect of Eicosapentaenoic Acid Supplementation on Paraoxonase 2 Gene Expression in Patients with Type 2 Diabetes Mellitus: a Randomized Double-blind Clinical Trial

Clinical Nutrition Research ◽

10.7762/cnr.2019.8.1.17 ◽

2019 ◽

Vol 8 (1) ◽

pp. 17 ◽

Cited By ~ 5

Author(s):

Mohammad Hassan Golzari ◽

Mohammad Hassan Javanbakht ◽

Ehsan Ghaedi ◽

Hamed Mohammadi ◽

Mahmoud Djalali

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Clinical Trial ◽

Type 2 Diabetes Mellitus ◽

Eicosapentaenoic Acid ◽

Double Blind ◽

Acid Supplementation ◽

Double Blind Clinical Trial

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17165866 ◽

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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