Laboratory of Molecular Biophysics Laboratory Journal 2001 Dr. K. A. Watson

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Kimberly A. Watson

Computational drug design and structural biology of insulin signalling proteins.

Type II diabetes is a familial disease but the genes that are involved have yet to be discovered. It is the common form of the disease that occurs in middle age. It occurs in 8% of those age 60-70yrs, and is usually treated with diet, exercise or tablets. Although it tends to be regarded as a "mild" form of diabetes, patients can develop complications such as heart attacks and strokes, which occur at least twice as commonly in diabetic patients as in the general population. It is the most common cause in middle age of blindness, amputations and kidney failure. It has been estimated that in the UK, approximately 11% of the total budget for healthcare is attributable to diabetes. Since the cause of the disease is not known, current treatments have been developed through chance discoveries. These are only weakly effective and the blood sugars usually remain high, and are a major contributing factor to the complications.

It is known that impaired ß-cell function is the major problem inducing progressive hyperglycaemia in Type II diabetic patients, thus it is important to elucidate the mechanisms involved in the regulation of insulin secretion. Our work directly addresses the interactions of proteins whose importance in insulin secretion and glucose homeostasis is becoming apparent. Current understanding of the control of insulin secretion is still sufficiently poor to allow structural characterisation of such regulatory proteins to make significant contributions to the emerging picture. In fact, many of the key regulating proteins have now been described in animals, but little is known about which of these proteins is important in man, and what is their contribution.

Currently, our studies are focused on proteins involved in liver and muscle glycogen metabolism (phosphorylase and glycogen synthase), the pancreatic ß-cell K⁺-ATP sensitive channel regulatory subunit (SUR1), and other signalling proteins of the pancreatic ß-cell (CD38, -endosulfine).

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