Scientists One Step Closer to Understanding Cause of Type 2 Diabetes
Study Sheds Light on Role of Insulin Receptors in Insulin Production
BOSTON — February 3, 1999 — A new study led by scientists at Joslin Diabetes Center provides new insights and a novel hypothesis for a unified cause of type 2 (adult onset) diabetes.
Type 2 diabetes affects an estimated 16 million people in the U.S., one-third of whom don't know they have the disease. In type 2 diabetes, tissues of the body such as muscle, liver and fat are resistant to the action of insulin, while the pancreas produces some, but not enough, insulin, to overcome this resistance. As a result, blood sugar (glucose) backs up in the bloodstream. If poorly managed over time, elevated blood sugar levels can lead to such complications as blindness, leg and foot amputations, kidney disease, heart disease and stroke. Type 2 diabetes is more common in people over age 40 who are obese, sedentary and have family members with the disease.
In a report appearing in this week's journal Cell, Joslin Research Director C. Ronald Kahn, M.D., and Joslin research fellow Rohit N. Kulkarni, M.D., Ph.D., and their colleagues studied islet cell function in specially bred, genetically-altered mice. In the experimental mice, the insulin receptor in the pancreatic beta cells was made inactive so the researchers could study the effect of insulin signaling and insulin receptors on beta cell function.
"Scientists have known for some time that beta cell dysfunction in the pancreas is an important cause of type 2 diabetes in people, but exactly how it is linked to the insulin resistance in type 2 diabetes has been unclear," said Dr. Kahn, the Mary K. Iacocca Professor of Medicine at Harvard Medical School. "Our study shows that insulin receptors and insulin action have an important role of sensing glucose in the beta cells of the pancreas. This suggests that defects in insulin signaling at the beta cell level may contribute to altered insulin secretion found in type 2 diabetes and add to the defect found in peripheral tissues that leads to diabetes.
"This study provides the first model in animal studies showing what happens when there is insulin resistance in the islet beta cell," Dr. Kahn continued. "Mice lacking the beta cell insulin receptor showed a loss of insulin secretion ability in response to glucose, similar to that observed in humans with type 2 diabetes. The mice showed progressively impaired glucose tolerance at they aged over six months."
The researchers' findings are similar to what occurs in people early in the course of type 2 diabetes in which there is both insulin resistance and reduced insulin secretion in response to glucose. While the researchers believe it is unlikely in people that this decrease is due to a genetic absence of the insulin receptor, combinations of acquired and genetic alterations in the receptor and signaling could be involved in this disease syndrome.
"Our model not only provides direct evidence that the insulin receptor in the pancreatic beta cell has a functional role, but suggests that insulin resistance in the beta cell may contribute to alterations in insulin secretion in type 2 diabetes, thereby creating a hypothesis for how the disease develops," said Dr. Kahn. "This should open up completely new avenues to treatment of this disease."
Funding for the study was provided by the National Institutes of Health and the Greenwall Foundation. Researchers from Vanderbilt University in Nashville, Tenn., also participated in the study.
Established in 1898, Joslin Diabetes Center in Boston is an internationally recognized leader in diabetes and endocrine disease treatment, research, and patient and professional education affiliated with Harvard Medical School. In addition to its headquarters in Boston's Longwood Medical Area, Joslin has affiliated treatment centers across the country.
