The insulin receptor (IR) and low-density lipoprotein receptor (LDLR) maintain glucose and lipid metabolism, respectively. Diabetes is associated with increased blood glucose, dyslipidaemia and increased risk of atherosclerosis. We hypothesise that interactions between IR and LDLR play a role in the atherosclerotic process in subjects with diabetes. Therefore, in this work we studied potential interactions between these two receptors. Our data show an intracellular and surface membrane-bound co-association of IR and LDLR. The co-association makes LDLR functionally poor in clearing extracellular LDL particles. A short 10 min exposure of cells to insulin disrupts the association between the two receptors and generates LDLR with higher LDL clearing activity without any change in protein expression. This co-association of LDLR with IR and their dissociation by insulin may be an important part of the regulatory mechanism of the normal physiological receptor function in a biological system. Modulation of receptor co-association is potentially a therapeutic target to reduce cardiovascular risk, and further studies are needed to investigate this possibility.

Background & objectives:Lipoprotein associated phospholipase A2 (Lp-PLA2) is an important risk predictor of coronary artery disease (CAD). This study was aimed to evaluate Lp-PLA2 activity and oxidized low density lipoprotein (oxLDL) in newly diagnosed patients of type 2 diabetes mellitus and to determine the correlation of Lp-PLA2 activity with oxLDL and plasma glucose levels.Methods:Blood samples were collected in patients with newly diagnosed type 2 diabetes (n=40) before any treatment was started and healthy controls (n=40). These were processed for estimating plasma glucose: fasting and post prandial, ox LDL, and Lp-PLA2 activity. The parameters in the two groups were compared. Correlation between different parameters was calculated by Pearson correlation analysis in both groups.Results:Lp-PLA2 activity (24.48 ± 4.91 vs 18.63 ± 5.29 nmol/min/ml, P<0.001) and oxLDL levels (52.46 ± 40.19 vs 33.26 ± 12.54 μmol/l, P<0.01) were significantly higher in patients as compared to those in controls. Lp-PLA2 activity correlated positively with oxLDL in both controls (r=0.414, P<0.01), as well in patients (r=0.542, P<0.01). A positive correlation between Lp-PLA2 activity and fasting plasma glucose levels was observed only in patients (r=0.348, P<0.05).Interpretation & conclusions:Result of this study implies that higher risk of CAD in patients with diabetes may be due to increase in Lp-PLA2 activity during the early course of the disease. A positive correlation between enzyme activity and fasting plasma glucose indicates an association between hyperglycaemia and increased activity of Lp-PLA2. This may explain a higher occurrence of CAD in patients with diabetes. A positive correlation between oxLDL and Lp-PLA2 activity suggests that Lp-PLA2 activity may be affected by oxLDL also.

ABSTRACT

Background MicroRNAs (miRNAs) represent a novel class of single-stranded RNA molecules of 18–22 nucleotides that serve as powerful tools in the regulation of gene expression. They are important regulatory molecules in several biological processes. Main body Alteration in the expression profiles of miRNAs have been found in several diseases. It is anticipated that miRNA expression profiling can become a novel diagnostic tool in the future. Hence, this review evaluates the implications of miRNAs in various diseases and the recent advances in miRNA expression level detection and their target identification. A systematic approach to review existing literature available on databases such as Medline, PubMed, and EMBASE was conducted to have a better understanding of mechanisms mediating miRNA-dependent gene regulation and their role as diagnostic markers and therapeutic agents. Conclusion A clear understanding of the complex multilevel regulation of miRNA expression is a prerequisite to explicate the origin of a wide variety of diseases. It is understandable that miRNAs offer potential targets both in diagnostics and therapeutics of a multitude of diseases. The inclusion of specific miRNA expression profiles as biomarkers may lead to crucial advancements in facilitating disease diagnosis and classification, monitoring its prognosis, and treatment. However, standardization of methods has a pivotal role in the success of extensive use of miRNA expression profiling in routine clinical settings.

Diabetes mellitus, a multifactorial pathology, is a growing health problem in developed and developing countries of the modern world. Genetic, ethnic, health, dietary habit, sedentary potential, gestational abnormality in addition to other environmental stress factors are the potential stimuli for precipitating diabetic patho-physiology. The chemistry of diabetes and its milieu are multi-directional and cross-connectable. Diabetes is inter-related to hypertension, obesity, atherosclerosis, cardio-arterial disease, stroke and cancer. All these diseases can be transformed from its own pathology to other through some common axle which is still unknown. Advances in modern medicine and biotechnology are in prudent use in global research to strip up the cellular mechanism and its exploitation to bring remedies of these metabolic diseases. The probes of genetic engineering and drug modelling to find less side effects with the advents of information technology, abolition of abnormal genetic messages by DNA/RNA interference and organ grafting with regenerative prostheses by stem cell exploration are among some of the delicate devices to encounter the enmities orchestrated by the inter-locks of these dreadful diseases. This review sieves the prevailing scenario of the disease and its interventions standing in the house of advancements in second decade of this 21 st century.