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Mike Cawthorne

Professor of Metabolic Diseases

Clore Laboratory

University of Buckingham

tel: +44 (0)1280 820309

mike.cawthorne@buckingham.ac.uk www.buckingham.ac.uk/clore

intake or inhibitors of nutrient (fat) absorption. Side effects have

been common and have, in a number of cases, led to the drugs

being withdrawn.

As indicated earlier, 80% of people

with diabetes (predominantly

Type 2) live in low and middle

income countries.

Scientists from the Clore Laboratory pioneered the idea of treating

obesity (and Type 2 diabetes) by activating increased energy

utilisation by brown adipose tissue. These compounds

3

-adrenoceptor agonists) failed because of species differences in

the ß

3

-adrenoceptor and the view that adult man lacked the target

tissue. The latter view has now been shown to be erroneous and a

new era of studies to develop thermogenic treatments has begun.

Drugs from plants

80% of people with diabetes (predominantly Type 2) live in low

and middle income countries. In high income countries, diabetes

is more prevalent in the lower social economic classes.

In Barbados, the Prime Minister has stated that all the economic

gains post-independence have been lost to the development of

chronic metabolic disease, of which diabetes is a major component.

It follows, therefore, that many countries and their populations will

never be able to afford developed world treatments, particularly

those that medical opinion leaders are advocating.

A potential solution to the problem is the identification of plant-

based treatments that could be put together in combination to

provide locally grown, defined plant extracts that would ideally

mirror, or more realistically approximate to, developed world drug

treatments. The Clore Laboratory is working on a number of such

agents which might also be used in the developed world for

preventing the progression to diabetes in people with pre-diabetes

(impaired glucose tolerance).

Methods of preclinical research

n

Well-validated rodent models;

n

Proof of concept studies;

n

Body composition measurements: DEXA and NMR;

n

Food intake measurements and diet choice;

n

Central administration;

n

Energy expenditure by indirect calorimetry;

n

Oral, intraperitoneal and i.v. glucose tolerance;

n

Insulin sensitivity measurements (glucose clamp and non-

clamp techniques);

n

Transgenic models;

n

Hepatic glucose uptake and tissue utilisation rates;

n

Pancreatic perfusion;

n

Isolated pancreatic islets, hepatocytes and adipocytes;

n

Isolated soleus muscle;

n

Pancreatic islet cell mass;

n

Immunohistochemistry;

n

Microarrays, RNA analysis and western blots;

n

Confocal microscopy;

n

FACS analysis and cell sorting; and

n

In silico

pathway analysis.

The Buckingham Institute of Translational Medicine

The University of Buckingham