Scientists in France and the United States report that a variant of a common protein plays a primary role in Type 2 diabetes and obesity, key features of the "insulin resistance syndrome" that affects more than 50 million people in this country and a similar number in Europe.
Incidence of the syndrome, also linked to coronary artery disease, high blood pressure and high cholesterol, is soaring in the United States and other developed countries. Some clinicians and researchers refer to the syndrome as the metabolic syndrome.
The new research result, based on a very large genetic study of French families, is reported in the August issue of Nature Genetics.
The study identifies a target protein for potential drugs to restore the body's ability to respond to insulin, says Dr. Ira Goldfine, a co-author of the study whose UCSF research team first detected the protein, known as PC-1, in abnormally high amounts in diabetes patients 10 years ago.
The same 1995 paper showed that the PC-1 protein inactivates another protein, called the insulin receptor, which binds insulin. Other work in the lab showed that when this inactivation occurs, it prevents insulin from regulating metabolism of glucose in diabetic people.
The new discovery opens up the possibility of developing drugs to prevent or reverse the potentially deadly insulin resistance syndrome, says Goldfine, professor of medicine at UCSF.
Evidence from many investigators indicates that the insulin resistance syndrome is caused by the body's inability to use insulin efficiently, often leading to obesity, high blood pressure, high cholesterol, and Type 2 diabetes. This syndrome doubles heart attack and stroke risk, and triples the likelihood of early death from either cause.
The new research was led by David Meyre and Philippe Froguel, leading French scientists in research on the genetics of obesity and diabetes, based at the Pasteur Institute's CNRS Institute of Biology in France. UCSF co-author along with Goldfine is Betty Maddux, a UCSF diabetes researcher who has collaborated with Goldfine on several key PC-1 studies.