scholarly journals PHARMACOLOGICAL EFFECT OF METFORMIN AND PIOGLITAZONE ON VISFATIN DERIVED FROM ADIPOCYTES IN PATHOGENESIS OF TYPE 2 DIABETES

2021 ◽  
pp. 162-165
Author(s):  
Madhukar Saxena ◽  
Yash Chikara ◽  
Mohseen Mohseen ◽  
Vandana Singh ◽  
Dinesh Raj Modi

Adipocytes secreate many adipocytokines including visfatin. Many evidence either in direct relation or in in vitro showed that visfatin alters the state of type 2 diabetes (T2DM).To unfold the role of visfatin in response to metformin and pioglitazone we have investigated the lipid profile and levels of visfatin along with its mRNA expression in response to antidiabetic drugs metformin and pioglitazone in vitro adipocytes.Adipocytes were cultured for the estimation of lipid profile and secreted visfatin using ELISA and the response of mRNA visfatin gene expression by the use of metformin hydrochloride and pioglitazone hydrochloride and combination of both.The determination was performed by RT- PCR quantification. Differences were considered significant when P values were ≤0.05 calculated using SPSS software (ver. 19).In Glucose treated adipocytes the lipid profile showed significant change in HDL while highly significant change in other lipoproteins.However,the released level of visfatin also showed significant change in glucose treated adipocytes as compared to normal control adipocytes. No significant change was observed in metformin hydrochloride while pioglitazone hydrochloride showed significant change as concurred by mRNA level estimation. The present report examined whether visfatin is regulated by anti-diabetic drugs metformin and pioglitazone in glucose feed adipocytes mimicking the state of T2DM along with effect of these drugs in secreted lipid profile. Pioglitazone treatment showed highly significant association at higher concentration. Our finding suggest that the treatment with pioglitazone in glucose treated adipocytes could play a role in the regulation of visfatin in adipocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Andrea S. Costa ◽  
Majed S. Alokail ◽  
Milena Zanzottera ◽  
Amal M. Alenad ◽  
...  

A possible role ofSnap25polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 inSnap25using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f=4.41,df=1, andp=0.03andf=5.31,df=1, andp=0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f=7.29,df=1, andp=0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p=0.01and OR: 1.05), HbA1c levels (OR: 5.06 andp=0.02), and lower insulinemia (p=0.03and OR: 0.95) in T2DM patients. The minorSnap25rs363050 (G) allele, which results in a reduced expression ofSnap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin.


2018 ◽  
Vol 5 (4) ◽  
pp. 969
Author(s):  
S. P. Tejaswi Pullakanam ◽  
Krishna Barla ◽  
Ramakrishna Nekkala ◽  
Pullaiah Pasupeleti

Background: Patients with diabetes are considered to be at high risk for dyslipidemia and hypertension and therefore vulnerable to cardiovascular diseases. This study describes the possible role of Glycated Hemoglobin (HbA1c) and serum lipid profile as a biomarker for detecting cardiovascular diseases. The aim of present work is to study the role of HbA1c as a screening biomarker for dyslipidemia in patients with type 2 Diabetes Mellitus (T2DM).Methods: Present study consists of 100 Type 2 DM patients between age 30-75 years along with age and sex matched 100 healthy controls. Fasting Blood samples were collected from all participants for measuring lipid profile, blood sugar (FBS) and HbA1c.Results: Present study revealed a significantly increased level of glycated hemoglobin (HbA1c) in cases compared to control. HbA1c showed direct and significant correlations with cholesterol, triglycerides and LDL and inverse correlation with HDL in cases when compared to controls.Conclusions: HbA1c can be used as a potential biomarker for the prediction of Dyslipidemia and CVD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Duyen Tran ◽  
Stephen Myers ◽  
Courtney McGowan ◽  
Darren Henstridge ◽  
Rajaraman Eri ◽  
...  

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. In vitro studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of in vitro assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.


2019 ◽  
Vol 15 (2) ◽  
pp. 100-104 ◽  
Author(s):  
Wendy Amy Ofosu ◽  
Dahir Mohamed ◽  
Olivia Corcoran ◽  
Opeolu Oyejide Ojo

Introduction: Challenges facing the treatment of type 2 diabetes necessitate the search for agents which act via alternative pathways to provide better therapeutic outcomes. Recently, an increasing body of evidence implicates the activation of oestrogen receptors (ERα and ERβ) in the development and treatment of underlying conditions in type 2 diabetes. This article summarizes available evidence for the involvement of oestrogen receptors in insulin secretion, insulin resistance as well as glucose uptake and highlights the potential of ERβ as a therapeutic target. Background: Recent studies indicate an association between the activation of each of the isoforms of ER and recent findings indicate that ERβ shows promise as a potential target for antidiabetic drugs. In vitro and in vivo studies in receptor knockout mice indicate beneficial actions of selective agonists of ERβ receptor and underscore its therapeutic potential. Conclusion: Studies are needed to further elucidate the exact mechanism underlying the role of ERβ activation as a therapeutic approach in the management of type 2 diabetes.


2014 ◽  
Vol 224 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Xiao-Bing Cui ◽  
Jun-Na Luan ◽  
Jianping Ye ◽  
Shi-You Chen

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.


2017 ◽  
Vol 5 (1) ◽  
pp. 153
Author(s):  
Arun Chaturvedi ◽  
Ankita Prakash ◽  
Ashutosh Bhardwaj ◽  
Rashmi Prakash ◽  
Sandeep Kharab

2010 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
Moola Joghee Nanjan ◽  
James Betz ◽  
◽  

Over the past 10 years more than 10,000 papers andin vitroinvestigations have been published that identify or analyse various critical pathways and biological processes through which the phytoalexin resveratrol has been shown to attenuate the metabolic dysfunctions, acute symptomatology and the consequential downstream pathologies related to type 2 diabetes. More recently, several clinical trials have confirmed resveratrol’s potential to substantially enhance the therapeutic effects of the pharmaceutical metformin hydrochloride, particularly related to glucose management, insulin sensitivity and cardioprotection. Metformin is the most commonly prescribed type 2 diabetes treatment worldwide; consequently, any compound with the ability to safely and effectively augment its therapeutic effects warrants intensive investigation. This paper elucidates the principal modes of action that underly resveratrol’s promising potential as an effective adjunct treatment for patients currently being administered metformin.


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