Type 1 Diabetes Reversed in Gene-engineered Mice


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Posted by Ellen on June 01, 2002 at 15:09:10:

Type 1 Diabetes Reversed in Gene-engineered Mice
Reuters Health

Thursday, May 30, 2002


NEW YORK (Reuters Health) - By boosting the production of a protein related to insulin, researchers in Spain have reversed type 1 diabetes in mice.

The study was carried out in genetically engineered mice, so it is uncertain whether the treatment will work in normal mice, much less in people. But the success does suggest that it might be possible to develop a gene therapy to treat type 1 diabetes, according to the study's authors.

Type 1 diabetes is sometimes called juvenile diabetes because it usually strikes at a younger age than the more common type 2 diabetes. In type 1 diabetes, the immune system launches a misguided attack against pancreatic cells called beta cells, which produce insulin. This leads to low or nonexistent levels of the sugar-regulating hormone. People with this type of diabetes must take daily insulin injections to survive.

To recover from type 1 diabetes, the body needs to have its supply of beta cells replenished. One experimental approach is to transplant islets, which are clusters of cells in the pancreas that contain beta cells. Unfortunately, the scarcity of donors and the risk that the immune system will destroy the transplanted cells limit this option.

A team at the Universitat Autonoma de Barcelona led by Dr. Fatima Bosch has developed a type of gene therapy that restores islets without a transplant of the cells.

Based on evidence that a substance called insulin-like growth factor-I (IGF-I) promotes the growth and development of pancreatic tissue, the researchers genetically engineered two strains of mice to overexpress the gene for IGF-I in beta cells. They then gave the mice multiple doses of a drug that triggers type 1 diabetes.

Not surprisingly, beta cells were destroyed and type 1 diabetes developed in both strains of genetically engineered mice. Eventually, however, the genetically engineered mice recovered, with the time varying depending on the strain of mice, according to a report in the May issue of The Journal of Clinical Investigation. Blood sugar levels, which initially rose, returned to normal, and the mice experienced a rebound in beta cells.

In contrast, a group of normal mice that had been exposed to the drug all developed diabetes and died.

Although most people are not diagnosed with type 1 diabetes until after symptoms--and the destruction of beta cells--are well under way, the study suggests that it might be possible to counteract the destruction of the insulin-producing cells by getting the pancreas to express factors, such as IGF-I, that encourage the growth of beta cells, according to the researchers.

"Our study suggests that IGF-I might be considered a candidate gene to be transferred to pancreatic islets as a new gene therapy approach for type 1 diabetes," Bosch's team concludes.

SOURCE: The Journal of Clinical Investigation 2002;109:1153-1163.

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