Targets For Type 2 Diabetes Mellitus Research Articles

Integrated computational approaches to screen gene expression data to determine key genes and therapeutic targets for type-2 diabetes mellitus

There is a rapid rise in cases of Type-2-diabetes mellitus (T2DM) globally, irrespective of the geography, ethnicity or any other variable factors. The molecular mechanisms that could cause the condition of T2DM need to be more thoroughly analysed to understand the clinical manifestations and to derive better therapeutic regimes. Tools in bioinformatics are used to trace out key gene elements and to identify the key causative gene elements and their possible therapeutic agents. Microarray datasets were retrieved from the Gene expression omnibus database and studied using R to derive different expressed gene (DEG) elements. With the comparison of the expressed genes with disease specific genes in DisGeNET, the final annotated genes were taken for analysis. Gene Ontology studies, Protein–protein interaction (PPI), Co-expression analysis, Gene-drug interactions were performed to scale down the hub genes and to identify the novelty across the genes analysed so far. In vivo and invitro analysis of key genes and the trace of interaction pathway is crucial to better understand the unique outcomes from the novel genes, forming the basis to understand the pathway that ends up causing T2DM. Afterwards, docking was executed enabling recognition of interacting residues involved in inhibition. The complex CCL5-265 and CD8A-40585 thus docked showed best results as is evident from its PCA analysis and MMGBSA calculation. There is now scope for deriving candidate drugs that could possibly detect personalized therapies for T2DM.

Will intestinal flora therapy become a new target in type-2 diabetes mellitus? A review based on 13 clinical trials.

Background: diabetes mellitus (DM) is a chronic disease and its pathogenesis is still inconclusive. Current evidence suggests an association between intestinal flora and type-2 diabetes mellitus (T2DM). In this paper, we summarized the current research, determining whether intestinal flora may become a new method to treat T2DM, and providing a theoretical basis and literature references for the prevention of T2DM based on the regulation of intestinal flora. Method: we carried out a review based on 13 published clinical trials to determine the correlation between T2DM and intestinal flora, and between changes in clinical outcomes and in intestinal flora in the development of T2DM; to assess the pathological mechanisms; and to discuss the treatment of diabetes based on intestinal flora. Results: we found that intestinal flora is involved in the occurrence and development of T2DM. Several pathological mechanisms may be involved in the process, including improving the gut barrier, alleviating inflammation, increasing glucagon-like peptide (GLP) 1 and GLP 2, increasing the production of short-chain fatty acids (SCFAs), and so on. Several measures based on intestinal flora, including exercise, food, specific diets, drugs and probiotics, would be used to treat and even prevent T2DM. Conclusions: high-quality studies are required to better understand the clinical effects of intestinal flora in T2DM.

Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) as A Therapeutical Target in Type-2 Diabetes Mellitus: A Review

BACKGROUND: Increasing free radicals and oxidative stress due to chronic hyperglycemia in type-2 diabetes mellitus (DM) promotes the activity of endogenic antioxidative genes. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and activity are important to regulate the production of endogenic antioxidative enzymes.CONTENT: Normally, Nrf2 is bound by protein Kelchlike ECH-associated protein-1 (Keap1) in the cytosol. Stimulation from oxidative stress causes the release of Nrf2 from Keap1. When activated, Nrf2 enters the nucleus and activates the antioxidant response element (ARE). This will further increase the production of antioxidative enzymes, such as catalase, nitrite oxydase and heme oxygenase-1. The discovery of oxidative stress, as the cause of complications in DM, gives rise to the idea of developing a treatment which can increase the expression and activity of Nrf2, one of which is a flavonoid antioxidant.SUMMARY: Currently, nuclear factor erythroid 2-related factor 2 is an important target in the therapy of DM.KEYWORDS: Nrf2, type-2 diabetes mellitus, endogenic antioxidative enzymes, oxidative stress, antioxidants

ChemInform Abstract: Synthesis of N4‐Aryl‐β‐D‐glucopyranosylcytosines: A Methodology Study.

Abstract A number of leaving groups, including arylsulfonates, triazoles, 3-nitrotriazoles, and tetrazoles, have been studied for the substitution reaction by aryl and alkyl amines at the 4-position of β- d -glucopyranosyluracils. Examination of the stability, ease of purification and reactivity in the substitution reaction led to a number of optimized conditions with the most convenient involving substitution of triazole derivatives under microwave conditions in the presence of silica gel. Under these conditions, a number of N4-aryl-substituted β- d -glucopyranosylcytosines were prepared as potential inhibitors of glycogen phosphorylase, a molecular target for type-2 diabetes mellitus.

Synthesis of N4-aryl-β-d-glucopyranosylcytosines: a methodology study

A number of leaving groups, including arylsulfonates, triazoles, 3-nitrotriazoles, and tetrazoles, have been studied for the substitution reaction by aryl and alkyl amines at the 4-position of β-d-glucopyranosyluracils. Examination of the stability, ease of purification and reactivity in the substitution reaction led to a number of optimized conditions with the most convenient involving substitution of triazole derivatives under microwave conditions in the presence of silica gel. Under these conditions, a number of N4-aryl-substituted β-d-glucopyranosylcytosines were prepared as potential inhibitors of glycogen phosphorylase, a molecular target for type-2 diabetes mellitus.