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

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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Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted Binding and Phosphorylation Inhibition of PPARγ

PPAR Research ◽

10.1155/2017/4313561 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 9

Author(s):

De-Si Pan ◽

Wei Wang ◽

Nan-Song Liu ◽

Qian-Jiao Yang ◽

Kun Zhang ◽

...

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Glucose And Lipid Metabolism ◽

Effective Part

Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called thiazolidinediones (TZD), which improve insulin resistance and glycemic control. Despite their effectiveness in treating diabetes, these drugs provide little protection from eminent cardiovascular disease associated with diabetes. Here we demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome proliferator-activated receptor (PPAR) pan agonist with moderate transcription activity, preferentially regulates ANGPTL4 and PDK4, which are involved in glucose and lipid metabolism. CDK5-mediated phosphorylation at serine 273 (S273) is a unique regulatory mechanism reserved for PPARγ, and this event is linked to insulin resistance in type 2 diabetes mellitus. Our data demonstrates that chiglitazar modulates gene expression differently from two TZDs, rosiglitazone and pioglitazone, via its configuration-restricted binding and phosphorylation inhibition of PPARγ. Chiglitazar induced significantly greater expression of ANGPTL4 and PDK4 than rosiglitazone and pioglitazone in different cell models. These increased expressions were dependent on the phosphorylation status of PPARγ at S273. Furthermore, ChIP and AlphaScreen assays showed that phosphorylation at S273 inhibited promoter binding and cofactor recruitment by PPARγ. Based on these results, activities from pan agonist chiglitazar can be an effective part of a long-term therapeutic strategy for treating type 2 diabetes in a more balanced action among its targeted organs.

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

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4550 ◽

2020 ◽

Vol 8 (A) ◽

pp. 629-632

Author(s):

Yetty Machrina ◽

Yunita Sari Pane ◽

Dharma Lindarto

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

High Intensity ◽

Metabolic Enzymes ◽

Moderate Intensity ◽

Metabolism Enzymes

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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Effect of sitagliptin on expression of skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α and irisin in a rat model of type 2 diabetes mellitus

Journal of International Medical Research ◽

10.1177/0300060519885569 ◽

2020 ◽

Vol 48 (5) ◽

pp. 030006051988556

Author(s):

Yuntao Liu ◽

Feng Xu ◽

Pan Jiang

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Tnf Α

Objective To evaluate the effect of sitagliptin on skeletal muscle expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), irisin, and phosphoadenylated adenylate activated protein kinase (p-AMPK) in a rat model of type 2 diabetes mellitus (T2DM). Methods A high-fat diet/streptozotocin T2DM rat model was established. Rats were divided into T2DM, low-dose sitagliptin (ST1), high-dose sitagliptin (ST2), and normal control groups (NC). PGC-1α, irisin, and p-AMPK protein levels in skeletal muscle were measured by western blot, and PCG-1α and Fndc5 mRNA levels were assessed by reverse transcription-polymerase chain reaction. Results Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment-insulin resistance (HOMA-IR), and tumor necrosis factor-α (TNF-α) were significantly up-regulated in the T2DM compared with the other groups, and FPG, FIns, total cholesterol, triglycerides, TNF-α, and HOMA-IR were significantly down-regulated in the ST2 compared with the ST1 group. PGC-1α, irisin, and p-AMPK expression levels decreased successively in the ST2, ST1, and DM groups compared with the NC, and were all significantly up-regulated in the ST2 compared with the ST1 group. Conclusion Down-regulation of PGC-1α and irisin in skeletal muscle may be involved in T2DM. Sitagliptin can dose-dependently up-regulate PCG-1α and irisin, potentially improving insulin resistance and glycolipid metabolism and inhibiting inflammation.

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