scholarly journals In-silico Analysis of Phenyl Propanoic Acid Derivatives to Design Potent Peroxisome Proliferator-activated Receptor (PPAR) Dual Agonists for Type 2 Diabetes mellitus Therapy

2018 ◽  
Vol 34 (3) ◽  
pp. 1400-1410
Author(s):  
Neha Verma ◽  
Usha Chouhan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
In Silico ◽  
In Silico Analysis ◽  
Propanoic Acid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Silico Analysis

scholarly journals IN SILICO ANALYSIS OF ACTIVE CONSTITUENTS OF SILYMARIN AS ΑLPHA-GLUCOSIDASE ENZYME INHIBITORS IN TYPE 2 DIABETES MELLITUS

2019 ◽  
pp. 225-229 ◽  
Author(s):  
AHMAD ZONOUBI ◽  
PRASHANTHA CN ◽  
D VISAGA PERUMAL ◽  
ZAHRA MAFIBANIASADI
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
In Silico ◽  
Enzyme Inhibitors ◽  
In Silico Analysis ◽  
Active Constituents ◽  
Alpha Glucosidase ◽  
Silico Analysis

Objective: Type 2 diabetes mellitus (T2DM) is an acute metabolic disorder, in which the vogue is increasing persistently globally. The maltase-glucoamylase/alpha-glucosidase inhibitor is an oral antidiabetic drug collectively, which is utilizing for regulating carbohydrates that ordinarily transformed into simple sugars and absorbed by the intestine. Researchers need to constantly explore alternative therapeutic strategies for the clinical management of DM due to the increased adverse event caused by conservative antidiabetic agents. The present study proposes a substitute drug to examine the seven bioactive phytocomponents of Silybum marianum (milk thistle) that can regulate the hyperglycemia by downregulating alpha-glucosidase and its activity. Methods: Different integrated web-based in silico tools and techniques were used to model the enzyme (receptor) as well as to determine the druggability of different active constituents of silymarin and their pharmacokinetics were predicted. Further, the active site of the enzyme was predicted followed by molecular docking method. Results: The results show silychristin A and silydianin having less carcinogenicity and strong interaction to the target protein (alpha-glucosidase) compare to the reference drugs (acarbose and miglitol) and these two molecules can be used for the best drug molecules in T2DM. Conclusion: In the proposed study, the in silico analysis helps researchers to utilize these compounds for clinical applications. The conclusion also suggests that synthetically and semi-synthetically, nucleus and peripheral modifications, either in the form of skeletal rearrangements or partial degradations as well as functional group addition and replacement of the active molecules present in silymarin giving access to new structural motifs, which can be used in future as a lead compounds for antagonising the alpha-glucosidase in the treatment of diabetes mellitus.

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

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.

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

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
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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