Sweet news for diabetics

Monday, 03 December, 2001

UTS scientists have made significant progress towards their goal of an effective gene-therapy treatment for diabetes that would make insulin injections obsolete.

Associate Professor Ann Simpson, who heads a research unit in the Cell and Molecular Biology Department, is the first researcher worldwide to identify and explain the mechanisms underpinning her team's previous achievement — the delivery of an insulin gene to liver cells to enable them to perform successfully the vital pancreatic functions of secreting and storing insulin.

Although the team's gene therapy strategy enabled liver cells to carry out pancreatic functions in addition to the co-existing liver cell functions, until now the mechanism involved has remained a mystery.

While it was known that insulin secretion in pancreatic beta cells was dependent on opening and closing potassium channels within these cells, Professor Simpson and Associate Professor Don Martin of Health Sciences established for the first time that similar channels in the liver cells hold the key to their adoption of pancreatic processes.

"These unique results, confirmed by confocal micrcoscopy undertaken by Dr Anne Swan of Sydney University, indicate that the expression of insulin in the liver cells has stimulated the activation of potassium-sensitive channels that are not normally seen in liver cells," Professor Simpson said.

"Previously, we knew how the beta cells in the pancreas worked but had no idea how the liver cells worked once we inserted the insulin gene and glucose transporters."

Professor Simpson's gene therapy research, which has relied on two liver cell lines specially engineered by her unit in collaboration with Professor Tuch for tissue culture research, has also extended to primary cell lines, those cells found in animals or humans. Recently, postdoctoral Fellow Dr Binhai Ren used a viral vector to deliver genes to primary liver cells in a live animal model. The results were encouraging for future experiments involving the delivery of the insulin gene to primary liver cells.

"The ideal situation would be to deliver the insulin gene efficiently to primary liver cells. But there are a lot of problems in engineering primary cells to secrete insulin. They are so delicate that techniques to deliver the gene to the laboratory cells kill the body cells," Professor Simpson said.

"If we elucidate exactly what we need to get a liver cell to secrete insulin in the liver cell model in the laboratory, then we have a better chance further down the track of engineering a primary liver cell to secrete insulin in the same manner."

If Professor Simpson and her team succeed in their objectives, it will be a major triumph for a diabetic treatment regimen that is drug-free — and switching on insulin production in a physiological way without drug stimulation has never been achieved before.

For more information go to the University of Technology, Sydney.

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