Researchers Find Possible Target To Prevent Type 1 Diabetes

Date: May 5, 2005

Neutralizing or blocking the actions of a specific protein could save children from developing type 1 diabetes.

In type 1 diabetes, the immune system goes awry, mistaking the patient’s own insulin-producing islet cells for foreign and potentially dangerous cells and destroying them. Diabetes patients face either a lifetime of insulin injections or a transplant of the islet cells that make insulin.

Now, researchers have identified an enzyme that appears to be necessary for the development of type 1 diabetes. This discovery could lead to development of a pharmaceutical that prevents the immune-mediated destruction of the islet cells that produce insulin.

A multi-institution team including Dr. Leonard Shultz, a senior staff scientist at The Jackson Laboratory, demonstrated that JNK2, a protein kinase enzyme, performs an essential function in the autoimmune process that destroys the islet cells. Many autoimmune diseases begin with the inappropriate activation of T cells—a type of white blood cell critical to the immune process. The researchers found JNK2 plays an important role in regulating the development of diabetogenic T cells. The research was conducted using mice bred by The Jackson Laboratory specifically as models of human diabetes.

Starting with mice that model type 1 diabetes, the scientists bred them with mice known to be genetically deficient in JNK2. They found lower levels of JNK2 protect against the spontaneous development of diabetes. To further test the function of JNK2, the team prepared spleen cells containing T cells from mice that produce the protein kinase JNK2 and mice lacking the JNK2 enzyme. Then they transferred these cells to non-diabetic mice and noted that a significantly lower level of diabetes occurred in the mice that received the spleen cells from the JNK2-deficient donors.

“Results of this study suggest JNK2 offers a pharmacological target for the design of JNK2 inhibitor drugs,” explained Dr. Shultz . “Such a drug could protect against type 1 diabetes by blocking the action of JNK2. Indeed, the pharmaceutical companies are already aware of some potential candidate drugs,” he said.

The findings are published in the May 10, 2005 edition of the Proceedings of the National Academy of Science (volume 102, number 19, pp. 6931-6935).

The Jackson Laboratory, founded 75 years ago, is the world's largest mammalian genetics research institution. Its research staff of more than 450 investigates the genetic basis of cancers, heart disease, osteoporosis, Alzheimer's disease, glaucoma, diabetes, and many other human diseases and disorders. The Laboratory is also the world's source for nearly 3,000 strains of genetically defined mice, home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.

# # #

Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes. Anja Jaeschke, Beth Doran, Judith Reilly and Roger J. Davis (Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School); Mercedes Rincon (Section of Immunology, Department of Medicine, University of Vermont Medical School); Donna Neuberg (Department of Biostatistical Science, Dana Farber Cancer Institute); Dale L. Greiner and Aldo A. Rossini (Program in Molecular Medicine and Division of Diabetes, Department of Medicine, University of Massachusetts); Leonard D. Shultz (The Jackson Laboratory); and Richard A. Flavell (Section of Immunobiology, Yale University School of Medicine).

Contact(s): Joyce Peterson, joyce@jax.org, 207-288-6058

For information on automatic email delivery of news releases (journalists only), please send an email request for details to news@jax.org.

Media Relations, Communications Office
The Jackson Laboratory
600 Main Street
Bar Harbor, Maine 04609-1500
Phone: 207-288-6051
Fax: 207-288-6076
Email: news@jax.org