Dr Manish Khanolkar has completed his specialist training in Diabetes and Endocrinology from the UK in 2009. He was awarded MD from Cardiff University for his work on ‘Effects of insulin sensitizing therapy on platelet, vascular function and blood pressure in type 2 diabetes’. He is currently employed as a Consultant Physician and Diabetologist at Auckland Diabetes Centre, NZ
Type 2 diabetes (T2D) is often associated with metabolic syndrome that is characterised by a peculiar dyslipidaemia comprising of elevated serum triglyceride levels in association with low HDL-Cholesterol levels (HDL-C). This disordered metabolic state leads to a build up of fatty acids in the liver and skeletal muscles, making these tissues resistant to the effects of insulin. The initial response of the body to insulin resistance is to increase insulin production that is effected by the beta cells of pancreas. Eventually, the beta cells are overwhelmed and can no longer produce enough insulin to maintain normoglycaemia, leading to the development of T2D. Peroxisome proliferator activated receptors (PPARs) are nuclear receptors that act as transcription regulators of various genes involved in energy metabolism. PPAR α and γ are the most studied and their agonists have been in use to treat both, T2D and dyslipidaemia. These agents have shown positive effects on multiple surrogate markers of cardiovascular disease. Furthermore, more recently, these agents have also demonstrated beneficial effects on hard clinical end points such as retinopathy as in the FIELD study. Although these metabolic benefits of PPAR agonists are mainly mediated through their genomic effects, our work has shown that some effects are potentially mediated through non-genomic effects as well. This is particularly well demonstrated in the enucleate platelet. We not only demonstrated the prescence of PPAR receptors in human platelets, but also that activating them has the potential to alter platelet aggregation and activation.
Masoumeh Karimpour is a PhD student at Umeå University working on non-targeted Gas Chromatography Mass Spectrometry methods focusing on effects of exposure on human metabolite profiles, mainly covering lipids, amino acids, sugars and organic acids
Biodiesel is a renewable fuel mainly consisting of esters, whereas petrodiesel is mainly paraffinic and aromatic. Replacing petrodiesel with biodiesel may have beneficial effects in ecology; however, public health effects are still unknown. In this project our goal was to study the effect of exposure to rapeseed methyl ester biodiesel and petrodiesel (DE) exhausts on human plasma metabolites. 19 non-smoking healthy males were exposed to DE or biodiesel exhaust for one hour in a randomized order. Peripheral blood was sampled at five time points: pre-exposure as well as two, four, eight and 24 hours post-exposure. A methanol/water based protocol was used on the plasma samples for extraction of low molecular compounds (<900 Da). This was followed by derivatization and analysis using gas chromatography coupled to time of flight mass spectrometry (GC-TOFMS). Using in-house script, data were processed which enabled identification and quantification of 73 metabolites, including 14 lipids. As a part of data analysis, univariate, ANOVA and multivariate analysis were used to examine the results and highlight metabolite, including lipid, profiles characteristic of each type of exposure in relation to its time of sampling. Preliminary results showed different responses in some lipid profiles e.g. octadecanoic acid after biodiesel exhaust exposure compared to DE exhaust exposure. To our knowledge, this is the first time that a randomized controlled trial followed by metabolomics analyses has been performed to investigate the effect of biodiesel exhaust exposure on human plasma metabolite/lipid profiles