Brain Enzyme May Regulate Appetite For Sugar Interview with:
Dr James Gardiner

Reader in Molecular Physiology
Imperial College Hammersmith Campus
London 0NN

Medical Research: What is the background for this study? What are the main findings?

Response: It is well known that glucose is a preferred food and is consumed in preference to other nutrients. Food intake is controlled by the brain in part this it is regulated by part of the brain called the hypothalamus.   Glucokinase is an important component of glucose sensing and is expressed in the hypothalamus and specifically in the arcuate nucleus. A hypothalamic mechanism regulating glucose intake has not previously been identified.

Using a rodent model we demonstrated that increasing glucokinase activity in the arcuate nucleus increased food intake and body weight. If glucose was available as separately then glucose intake is increased but not weight. Decreasing glucokinase activity in the arcuate nucleus had the opposite effect, reducing glucose intake when it was available.   Our results suggest that glucokinase controls glucose appetite and hence the amount of glucose consumed. This is the first time a mechanism controlling the intake of a specific nutrient has been described.

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Supplement May Reduce Cardiovascular Risks Linked to NSAIDS Interview with:
Dr. Jane A. Mitchell
National Heart and Lung Institute
Imperial College, London, UK

Medical Research: What is the background for this study? What are the main findings?

Dr. Mitchell: Anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme COX-2. COX-2 selective anti-inflammatory drugs, like Vioxx, were introduced to reduce gastrointestinal side effects associated with these drugs. However, COX-2 inhibitors as well as most older NSAIDs are associated with increased risk of heart attacks although the precise mechanisms underlying these side effects are not completely understood.

The main findings of this study are:

1) COX-2 is highly expressed in the kidney where its genetic deletion leads to changes in more than 1000 genes.

2) Analysis of these genes revealed changes in 2-3 specific genes that regulate levels of ADMA, an endogenous inhibitor of the nitric oxide released by vessels, that can be reversed by giving more of the substrate for NO, L-arginine.

3) Further studies showed that ADMA was indeed increased in the plasma of mice where COX-2 gene was knocked out or in normal mice given a COX-2 inhibitor.

4) In mice where COX-2 was knocked out the release of nitric oxide from vessels was reduced and this could be reversed by supply L-arginine.

5) ADMA was also increased in human volunteers taking a COX-2 inhibitor

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Controlling Insulin Release With Photoswitchable Sulfonylurea

Dr. David Hodson PhD Faculty of Medicine, Department of Medicine Imperial College Interview with:
Dr. David Hodson PhD
Faculty of Medicine, Department of Medicine
Imperial College London

Medical Research: What is the background for this research?

Dr. Hodson: Type 2 diabetes represents a huge socioeconomic challenge. As well as causing significant morbidity due to chronically elevated glucose levels, this disease is also a drain on healthcare budgets (~$20billion in the UK per year). While current treatments are effective, they are sometimes associated with side effects, usually due to off-target actions on organs such as the heart and brain. In addition, the ability to regulate blood glucose levels more tightly may decrease complications stemming from type diabetes (e.g. nerve, kidney and retina damage). As a proof-of-principle that the spatiotemporal precision of light can be harnessed to finely guide and control drug activity, we therefore decided to produce a light-activated anti-diabetic. Continue reading