Department of Diabetes and Cardiovascular Science
The Department, based at the Centre for Health Science in Inverness, is conducting extensive research, primarily into the causes and consequences of diabetes, but also into a wide range of clinical conditions; most notably cardiovascular diseases, inflammatory diseases, and cancer. Led by Professor Ian Megson, the mission of the department is to undertake world class research into the causes and treatment of diabetes and the cardiovascular diseases that the condition precipitates. The department also undertakes a range of contract research to support commercial entities of any size.
The department is also home to the Free Radical Research Facility, and has research expertise in genetics and immunology, and lipidomics.
Free radical research
Free radicals play crucial roles in human physiology and disease progression. Our interests focus on nitric oxide (NO), a potentially protective agent when produced in the correct quantities in the right place and at the right time, and oxygen-centred radicals that are generally regarded to be damaging and cytotoxic. In healthy individuals, the potentially toxic effects of oxygen-centred radicals are countered by a battery of antioxidant defences.
Imbalance in free radical production in favour of harmful radicals is a feature of diabetes that might be fundamental in many of the worst aspects of the disease. We are currently involved in a number of projects to investigate the cellular mechanisms that underlie free radical production, the link to inflammatory processes that exacerbate the harmful effects, and antioxidant and nutritional interventions that might help to manage these consequences. Ongoing projects link closely with the Genetics and Immunology Group and the Lipidomics Research Facility within the Department of Diabetes and Cardiovascular Science, and those that require input from patients utilise the adjacent Highland Clinical Research Facility.
Ongoing contract research is centred on measurement of a wide range of metabolites and markers in biological samples, with a special focus on those associated with oxidative stress and inflammation. The Free Radical Research Facility team is fortunate to occupy a brand new laboratory in the Highland Diabetes Institute, Centre for Health Science. The laboratory hosts the very latest technology for measuring free radicals and their characteristic cellular ‘footprints’. We also conduct functional studies in vitro and in vivo to establish the impact of new therapeutics at both the cellular level and in terms of clinical measures.
Free radical research activity
- The antioxidant properties and clinical potential of N-acetylcysteine as an antithrombotic therapeutic in type-2 diabetes.
- The mechanism of action and therapeutic potential of phytochemicals in diabetes and cardiovascular conditions.
- The role of intermediates in formation of advanced glycated end product in oxidative stress related to type-2 diabetes.
- The mechanism of action of endocannabinoids in platelet function
- The anti-inflammatory and antioxidant properties of oats in patients with type-2 diabetes.
- The relevance of plasma nitrite as a marker of endothelial function.
- The mechanism of action and potential therapeutic targets for novel nitric oxide donor drugs linked to nano-dots.
- The role of oxidative stress in nanoparticle toxicity.
- The role of oxidative stress in the cardiovascular effects of pollution.
- The biological actions and clinical potential of hybrid nitric oxide donor drugs in cardiovascular diseases and diabetes.
Genetics and immunology
The Genetic and Immunology Group (GIG) has a background in the mental health arena and is using molecular genetics, molecular biology, epigenetics and immunological techniques to investigate pathways common to schizophrenia, diabetes and the impact of medication of metabolism.
We are investigating these diverse conditions through two main avenues. Firstly we are interested in the biology of lipid-based signaling and inflammation [link to niacin and aspirin project]. Secondly we are investigating the interplay between environment and disease, particularly though adverse immune responses to diet. Some types of wheat gluten proteins may be involved in type-1 diabetes and schizophrenia.
Identification of the principal toxic gluten will lead to better understanding of immunogenetic mechanism of these diseases. Nutrigenomics is a new field, which studies the interaction between the way our genes operate and our dietary intake. We strongly believe the immune system plays a central role in bridging the link between our genetic make-up and toxic proteins from daily foods. Therefore our research work will benefit to everybody worldwide and will influence agricultural and food industries.
Identification of susceptibility genes and risk factors, as well as simple tests (biomarkers) that measure these traits will allow for prediction, treatment and prevention of these conditions. To achieve these goals the GIG has a modern genetics lab, and shares the top class laboratories of biochemistry and cytology as well as the Free Radical Research Facility.
Genetics and immunology current activity
- The genetic association between diabetes and schizophrenia
- Investigation of the gluten component toxic for health
- Study of antipsychotics-induced metabolic syndromes and diabetes
- Development of HLA-based tagging genotyping technology
- Isolation and detection of proline-specific proteases from bacteria living in the oral cavity
- Immunogenetic mechanism of schizophrenia and type-1 diabetes
- Investigation of the gluten component toxic for schizophrenia and diabetes
- Study of biomarkers for personalised medication
- Genetic analysis of type-2 diabetes in a large Caucasian population
- Biobanks for schizophrenia, diabetes and cardiovascular disease
Ongoing postgraduate projects
Colette Mustard: Studies on molecular mechanism of antipsychotics-related metabolic disorders
Andrew Shaw: The impact of glucose excusion on oxidative stress and inflammation in diabetes
Our ability to measure and identify substances in the blood is expanding at a phenomenal rate. Until recently, we did not have the technology to measure more than a handful of compounds at any one time. However, a new group of disciplines is growing around powerful analytical techniques and computational processing that allows us, at least in theory, to measure all the metabolites in a sample simultaneously (“metabolomics”). The importance of lipids as signalling molecules and markers of disease progression is only just emerging and the discipline of “lipidomics” has been adopted by only a few institutions worldwide to date.
The mission of the Lipidomics Research Facility at UHI is to become a world-class research facility in this field, with a particular emphasis on diabetes and cardiovascular disease, with obvious links to the other Research Groups within the Department of Diabetes and Cardiovascular Science. The thrust of the research will be to identify the role of lipid-based biomarkers in disease progression and to characterise new biomarkers that might help to identify at-risk individuals before they develop disease. This £2M development is now fully functional.