Recent Research Areas

Overview

This internationally recognised research group, housed in the purpose-built Clore Laboratory at the University of Buckingham, has interests in molecular genetics, biochemistry, pharmacology, nutrition and the physiology of metabolic diseases, particularly diabetes and obesity.

The Clore Laboratory has researchers with a track record in drug discovery, including beta3-adrenoceptor agonists for obesity, orexin and MCH-antagonists and the insulin sensitiser drug rosiglitazone.

Type 2 diabetes affects more than 300 million people worldwide and the number is expected to grow over the next 10 years. In Europe, 8-12% of the adult population have diabetes. In the United States, diabetes is the sixth highest cause of death by disease, with an estimated 16 million Americans affected. The incidence rates in many countries in the Middle East, the Indian subcontinent, South East Asia and South America are considerably higher than in Europe and North America, and in some cases are reaching epidemic levels.

Diabetes increases the risk of death from cardiovascular disease such as stroke, coronary heart disease and atherosclerosis. Diabetes is also the leading cause of adult-onset blindness, kidney failure, non-traumatic limb loss, and loss of neurosensory function.

Obesity is strongly linked with type 2 diabetes but it also impacts on many other diseases, particularly cardiovascular disease. Obesity is one of the fastest growing epidemics in the world, affecting both developed and developing countries. It is estimated that the costs of obesity represent approximately 6-8% of the direct healthcare budgets of developed countries. Obesity is not simply a matter of overeating; understanding obesity involves understanding the interaction of genes and diet and the complex neuroendocrine matrix that regulates energy balance.

The Clore Laboratory, University of Buckingham, has developed a sufficient critical mass of researchers to be able to study type 2 diabetes and obesity from the gene through to whole-body physiology. Our goal is to define new molecular targets that could be sites for novel pharmacology and to examine the therapeutic potential of pioneering agents acting at appropriate molecular targets.

Islet cell proliferation

Pioneering studies are being undertaken to examine factors that regulate islet cell mass as a potential novel approach to the treatment of diabetes.

Plant treatments for syndrome X (metabolic syndrome), obesity and diabetes

More than half of the diabetics in the world are treated by plant-based therapies. Studies are being undertaken to examine the mechanism of action of key plant-based treatments for these diseases and to evaluate their therapeutic potential compared with synthetic drugs.

Thermogenic receptors in muscle and adipose tissue

Stimulating thermogenesis remains a therapeutic goal in the worldwide fight to treat and prevent obesity. In addition to exercise, energy can be wasted by non-shivering thermogenesis. Studies at the Clore Laboratory are focusing on the identification of the role of uncoupling proteins and various beta-adrenoceptor subtypes in skeletal muscle and adipose tissue. A novel receptor that is functionally coupled to increased oxidative metabolism is being characterised. In addition, the interaction of this oxidative pathway with mitochondrial uncoupling proteins is being examined.

Transcriptional factors associated with insulin sensitivity and lipid metabolism

New agents to improve insulin sensitivity are being developed by pharmaceutical companies. These agents affect the transcription of insulin-responsive genes through activation of nuclear hormone receptors. Proof of principle studies are being conducted on pioneer therapeutics together with more fundamental studies to identify the mechanism of action of these pioneer compounds.

Leptin signalling in peripheral tissues

Leptin, the product of the ob gene, is secreted from adipose tissue and acts on central receptors to affect feeding and energy expenditure. It is hypothesised that leptin is a primary adipostat signal. The Clore Laboratory has shown also that leptin has effects on a number of peripheral tissues, including pancreatic islets, skeletal muscle and intestinal epithelial cells. In pancreatic islets leptin inhibits insulin secretion. Current studies are examining leptin signalling processes in pancreatic islets and the possibility that leptin may have islet protective effects.

Target validation and pioneer therapeutics for metabolic disease

The Clore Laboratory has particular skills in evaluating the therapeutic potential of pioneering therapies in the area of metabolic disease.

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