Published online 23 November 2000 | Nature | doi:10.1038/news001123-9

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Virus hope for diabetics

Peptide linked insulinPeptide linked insulin

Diabetic rats go into remission five days after being given a new gene, paving the way for clinical trials of the therapy. If effective in humans, this gene therapy would mean the end of frequent insulin injections and occasional dangerous comas for diabetes sufferers.

Ji-Won Yoon at Yonsei University, Seoul, Korea, and his colleagues have cured rats with diabetes by engineering them to produce a reasonably efficient insulin analogue - and, crucially, to produce it in response the levels of glucose in their blood1.

The team delivers the insulin gene by infecting rodents with a virus that is genetically modified so that it cannot spread or damage infected cells.

Diabetics produce insufficient insulin due to a malfunction in the beta cells of their pancreas. Insulin is the hormone that regulates blood sugar levels. Normally beta cells rapidly release insulin into the blood in response to changes in blood glucose concentration.

Insufficient blood glucose causes the body to run out of energy. Too much and the blood thickens, putting more stress on the heart, and increasing the risk of a stroke.

There are two types of diabetes. Type 2, the most common form, is caused by diet. It primarily affects overweight people in middle age, and is becoming increasingly common in wealthy western countries. Type 1, the genetic form of diabetes, starts in childhood or teenage years and affects about three people in every thousand.

At present, both types are treated with manual insulin injections or continuous pump-released insulin. But these therapies are disruptive to patients' lives. And their effects are clumsy: glucose and insulin levels cannot be adjusted moment by moment as they are in a healthy body by beta cells.

Patients often reject grafts of insulin-producing cells and efforts to regenerate healthy beta cells have not been successful. Gene therapy thus offers much-needed hope.

"Our gene therapy strategy could be applied to some patients with type 2 diabetes as well, as the defect is also in insulin production, but this remains to be tested," Yoon adds.

Jerrold M. Olefsky, who works on diabetes at the University of California, San Diego, is amazed the gene therapy worked so well, despite the fact that the insulin response to high blood glucose is slower in treated diabetic animals than in healthy animals.

Apparently, because the response is closely coupled to blood glucose, it is preferable to existing regular-dose therapies, even if it is more sluggish than normal. 

  • References

    1. Lee, H. C. , Kim, S.-J. , Kim, K.-S. , Shin, H.-C. & Yoon, J.-W. Remission in models of type I diabetes by gene therapy using a single-chain insulin analogue. Nature 408, 483-488 (2000). | Article | PubMed | ISI | ChemPort |