NIH Press Release
NATIONAL INSTITUTES OF HEALTH
National Institute of Child Health
and Human Development

FOR RELEASE
Friday, Feb. 21, 1997

Birgit An der Lan
(301) 493-4541
Clarissa Wittenberg
(301) 496-5135

Genetically Engineered Mouse Model For Diabetes Developed

A team of researchers from the Joslin Diabetes Center at Harvard, the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK), and the National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) have genetically engineered a diabetic mouse by disrupting genes that are essential for insulin action. A report of this work, authored by Jens Brüning, Jonathan Winnay, Susan Bonner-Weir, Simeon Taylor, Domenico Accili, and Ronald Kahn, appears in the February 21 issue of Cell.

These mice are resistant to insulin and become diabetic in adulthood, and are thus a model for adult-onset diabetes, the type of diabetes known as non-insulin-dependent diabetes mellitus (NIDDM) or type II diabetes. It is estimated that the disease affects five percent or more of this country's population; however, some degree of insulin resistance, that is, a requirement for large amounts of insulin to control blood glucose, is thought to affect as much as 25 percent of the population and to predispose such individuals to overt diabetes later in life. Older people who are overweight are particularly at risk for NIDDM. Genetic studies have suggested that, although NIDDM tends to run in families, the disease may be due to multiple genetic defects.

To obtain this mouse model, the researchers mated two mice, each bearing a genetic defect in the string of metabolic events that normally allows insulin to interact with cells. While only a few of the mice with the individual gene defects become diabetic, about half of the offspring that bear both defects do.

This work is important because it shows that, although mild genetic defects in the pathway of insulin action by themselves don't necessarily lead to diabetes, the interaction of the two defects is quite likely to lead to NIDDM. The broader implication is that a similar model may apply to other common disorders such as hypertension and cancer.

Insulin keeps blood glucose levels within defined limits by controlling the uptake and storage of glucose in liver, fat, and muscle cells. Large fluctuations in blood glucose are the cause of the devastating long-term complications of diabetes, such as damage to kidney and heart. Doctors do not yet know where the molecular defects lie in human NIDDM, and there is no cure for the disease. There is thus an urgent need for animal models, both to investigate the pathogenesis of NIDDM and to develop new therapies.