Sushma Verma

Bio: Sushma Verma is an academic researcher from University of Lucknow. The author has contributed to research in topics: Medicine & Genotype. The author has an hindex of 4, co-authored 9 publications receiving 39 citations.

Antioxidant enzyme levels as markers for type 2 diabetes mellitus

Abstract: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by increased production of free radicals and oxidative stress. Oxidative stress can be defined as an imbalance between the removal of free radical production and altered activity levels of antioxidant enzymes. The aim of this study was to evaluate the antioxidant enzyme activity such as superoxide dismutase (SOD), catalase (CAT) and glutathione S transferase (GST) in T2DM patients and healthy subjects in a North Indian population. The study was conducted on 474 T2DM and 301 healthy subjects. Blood lysates were prepared and levels of antioxidant enzymes viz. SOD, CAT and GST were measured by spectrophotometric method. Data were analyzed by using Prism software (v 5.01) and expressed as Mean ± SE. The activity levels of SOD and GST were significantly lower in T2DM patients than in healthy subjects (P<0.05) whereas that of catalase was higher in T2DM patients (15.56±1.53 units/mg) than in healthy subjects (12.12±1.212 units/mg). Analysis of data also showed that enzyme activity levels decreased with increasing age both in normal and T2DM conditions. Only GST level showed significant decrease in diabetic males while both GST and SOD decreased in diabetic females. Assay of enzyme activity levels in erythrocytes could be used as markers to identify individuals predisposed to T2DM.

PS 04-25 ASSOCIATION OF TCF7L2 AND PPARγ GENE VARIANTS WITH TYPE 2 DIABETES MELLITUS IN NORTH INDIAN POPULATION

Abstract: Objective: To determine the association of biochemical parameters and genetic polymorphisms in Transcription factors 7 like 2 (TCF7L2) and peroxisome proliferator-activated receptor-&ggr; (PPAR&ggr;) genes with Type 2 Diabetes Mellitus (T2DM) in north Indians. Design and Method: Subjects (n = 442) from North India were subjected to anthropometric, biochemical tests and genotyped for 4 different SNPs in TCF7L2 and PPAR&ggr; genes. Specific primers and restriction enzymes were used for polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) respectively. Statistical analyses were done by SPSS (v. 21.0) and SHEsis (v. online). Results: Blood glucose, cholesterol, blood pressure systolic, blood pressure diastolic, low density lipoprotein, serum creatinine were significantly increased while High-density lipoprotein and Very low density lipoprotein showed significant decrease in T2DM cases when compared to controls (P < 0.005). The frequency of ‘TT’ genotype of TCF7L2 rs7903146 (C/T) polymorphism was significantly lower in cases as compared to controls (P < 0.004, OR 0.34). ‘T’ allele of TCF7L2 rs7903146 (C/T) prevalence was significantly lower in cases as compared to controls (P < 0.03, OR 0.78). Individuals with ‘AG’ genotype of PPAR&ggr; gene rs11128600 (A/G) showed 1.13 times higher risk. PPAR&ggr; SNP rs17036314 (C/G) was monomorphic and TCF7L2 rs12255372 (G/T) did not show association in our population. The individuals with genotypic combinations with GG/CC (+/-, +/+) and GG/CT (+/-, +/+) of TCF7L2 SNPs showed slightly higher risk of T2DM whereas TG/TT (-/+) genotype frequency was significantly higher in controls. Conclusions: Our results suggested that TCF7L2 gene polymorphisms showed significant association with type 2 diabetes and the ‘T’ allele of rs7903146 (C/T) in TCF7L2 gene showed a protective role against T2DM in the study population.

A review of the molecular mechanisms of hyperglycemia-induced free radical generation leading to oxidative stress.

Abstract: The prevalence of diabetes is growing worldwide with an increasing morbidity and mortality associated with the development of diabetes complications. Free radical production is a normal biological process that is strictly controlled and has been shown to be important in normal cellular homeostasis, and in the bodies response to pathogens. However, there are several mechanisms leading to excessive free radical production that overcome the normal protective quenching mechanisms. Studies have shown that many of the diabetes complications result from excessive free radical generation and oxidative stress, and it has been shown that chronic hyperglycemia is a potent inducer for free radical production, generated through several pathways and triggering multiple molecular mechanisms. An understanding of these processes may help us to improving our preventive or therapeutic strategies. In this review, the major molecular pathways involved in free radical generation induced by hyperglycemia are described.

Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review.

Abstract: Diabetes mellitus is a metabolic disorder that majorly affects the endocrine gland, and it is symbolized by hyperglycemia and glucose intolerance owing to deficient insulin secretory responses and beta cell dysfunction. This ailment affects as many as 451 million people worldwide, and it is also one of the leading causes of death. In spite of the immense advances made in the development of orthodox antidiabetic drugs, these drugs are often considered not successful for the management and treatment of T2DM due to the myriad side effects associated with them. Thus, the exploration of medicinal herbs and natural products as therapeutic sources for the treatment of T2DM is promoted because they have little or no side effects. Bioactive molecules isolated from natural sources have been proven to lower blood glucose levels via regulating one or more of the following mechanisms: improvement of beta cell function, insulin resistance, glucose (re)absorption, and glucagon-like peptide-1 homeostasis. In recent times, the mechanisms of action of different bioactive molecules with antidiabetic properties and phytochemistry are gaining a lot of attention in the area of drug discovery. This review article presents an update of the findings from clinical research into medicinal plant therapy for T2DM.

Reactive metabolites and antioxidant gene polymorphisms in Type 2 diabetes mellitus

Abstract: Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) interactions with lipids, proteins and other mechanisms of human body. Production of RMs mainly superoxide (O2(-)) has been found in a variety of predominating cellular enzyme systems including NAD(P)H oxidase, xanthine oxidase (XO), cyclooxygenase (COX), uncoupled endothelial nitric oxide synthase (eNOS) and myeloperoxidase (MPO). The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product (AGE) formation; activation of protein kinase C (PKC) isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), nitric oxide synthase (NOS) are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in pathogenesis of T2DM individuals. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiate stress related pathways thereby leading to insulin resistance and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.

Enzymatic antioxidant system in vascular inflammation and coronary artery disease.

Abstract: In biological systems there is a balance between the production and neutralization of reactive oxygen species (ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis. Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease (CAD). Some observation indicated that in the early stages of the disease there is a homeostatic up-regulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage. As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.