Professor Ann Burchell

The liver is the main organ involved in the homeostatic regulation of blood glucose levels. When blood glucose levels are low the liver releases glucose into the bloodstream for use by other tissues, e.g. brain. In liver, glucose is produced inside the lumen of the endoplasmic reticulum by the glucose-6-phosphatase system. Substrates and products of the enzyme therefore need to cross the endoplasmic reticulum membrane.

My main research interest is the role of glucose-6-phosphatase in the regulation of blood glucose levels. My approach has been to purify and clone the proteins needed for normal glucose-6-phosphatase activity. To use the characterised proteins as a source of information and monospecific antibodies and then to use these tools to study the more complex problems posed by the system's biogenesis, regulation and genetic deficiencies. Hepatic glucose production and glucose-6-phosphatase activity are abnormally high in diabetes mellitus and abnormally low in many premature infants, but very little is known about the mechanisms by which glucose-6-phosphatase activity is regulated. We are investigating the mechanisms of hormonal (and drug) regulation of all the proteins of the glucose-6-phosphatase system during development and in a variety of metabolic (including diabetic) conditions. Recent work has centred on the regulation and genetic deficiencies of the glucose-6-phosphatase enzyme and glucose-6-phosphate transporter genes.

The main aims of the research are to:-

• determine which of the glucose-6-phosphatase proteins are the sites of disturbed function in diabetes and prematurity,
• determine whether any of the regulatory features of the glucose-6-phosphatase system can be exploited to achieve pharmacological management of hepatic output of glucose
• determine the molecular basis of the type 1 glycogen storage diseases. d) develop new improved treatments for type 1 glycogen storage disease.

Publications

Maintained by: H Murphie.

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