Saving the islets

An international collaboration between Canadian, French and American scientists could make early-onset Type 1 diabetes a thing of the past.

In the Type I form of diabetes, the so-called beta cells found in the pancreas manufacture too little or no insulin and the result is inadequate control of carbohydrate metabolism. If the disorder is left untreated, the concentration of glucose in the blood rises to abnormally high levels (hyperglycemia) after meals and in the long term causes blindness as well damage to nerves, blood vessels, and the kidneys.

The common treatment involves regular injections of the protein insulin, which are rather unpleasant as well as meaning sufferers always have to have sterile equipment and vials of insulin with them.

An important factor associated with the development of Type 1 diabetes is that the levels of Natural Killer T (NKT) cells in the immune system are lower than normal. The compound alpha-galactosylceramide (alpha-GalCer) binds to receptors on NKT-cells called CD1d receptors, and stimulates the production of cell-signalling molecules from NKT-cells.

When the researchers administered alpha-GalCer to laboratory mice, they found that it protected these mice from developing diabetes. It did so even when given after the immune system began its attack on the insulin-producing beta cells in the islets of the pancreas. Islet transplants are sometimes required by patients with type 1 diabetes to restore the number and function of their islet beta cells. Such patients usually need to take anti-rejection drugs for the remainder of their lives to prevent a further immune assault on their islet beta cells. The team found that the alpha-GalCer treatment prolonged the survival and function of islets transplanted into newly diabetic mice, and that it was unnecessary to treat the mice with any insulin or anti-rejection drugs.

	Crystal clear insulin (courtesy of NASA)

The collaborators, who include Terry Delovitch of the John P. Robarts Research Institute and University of Western Ontario in London, Ontario, Canada, Jean-Francois Bach of the Hopital Necker in Paris, France and Luc Van Kaer of Vanderbilt University in Knoxville, Tennesee, USA, suggest that alpha-GalCer might decrease the destruction of islet cells by the body's own immune system, which is thought to occur during the onset of diabetes. It could, therefore, provide benefit to diabetic patients.

Nature Medicine, 2001, 7(9), 1052^* and 1057^*

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