UT Southwestern researchers uncover potential 'cure' for type 1 diabetes

Type 1 diabetes could be converted to an asymptomatic, non-insulin-dependent disorder by eliminating the actions of a specific hormone, new findings by UT Southwestern Medical Center researchers suggest.

These findings in mice show that insulin becomes completely superfluous and its absence does not cause diabetes or any other abnormality when the actions of glucagon are suppressed. Glucagon, a hormone produced by the pancreas, prevents low blood sugar levels in healthy individuals. It causes high blood sugar in people with type 1 diabetes.

"We've all been brought up to think insulin is the all-powerful hormone without which life is impossible, but that isn't the case," said Dr. Roger Unger, professor of internal medicine and senior author of the study appearing online and in the February issue of Diabetes. "If diabetes is defined as restoration of glucose homeostasis to normal, then this treatment can perhaps be considered very close to a 'cure.' "

Insulin treatment has been the gold standard for type 1 diabetes (insulin-dependent diabetes) in humans since its discovery in 1922. But even optimal regulation of type 1 diabetes with insulin alone cannot restore normal glucose tolerance. These new findings demonstrate that the elimination of glucagon action restores glucose tolerance to normal.

Normally, glucagon is released when the glucose, or sugar, level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which directs the body's cells to remove sugar from the bloodstream.

Dr. Unger's laboratory research previously found that insulin's benefit resulted from its suppression of glucagon.

In type 1 diabetes, which affects about 1 million people in the U.S., the pancreatic islet cells that produce insulin are destroyed. As a countermeasure to this destruction, type 1 diabetics currently must take insulin multiple times a day to metabolize blood sugar, regulate blood-sugar levels and prevent diabetic coma. They also must adhere to strict dietary restrictions.

In this study, UT Southwestern scientists tested how mice genetically altered to lack working glucagon receptors responded to an oral glucose tolerance test. The test – which can be used to diagnose diabetes, gestational diabetes and prediabetes – measures the body's ability to metabolize, or clear, glucose from the bloodstream.

The researchers found that the mice with normal insulin production but without functioning glucagon receptors responded normally to the test. The mice also responded normally when their insulin-producing beta cells were destroyed. The mice had no insulin or glucagon action, but they did not develop diabetes.

"These findings suggest that if there is no glucagon, it doesn't matter if you don't have insulin," said Dr. Unger, who is also a physician at the Dallas VA Medical Center. "This does not mean insulin is unimportant. It is essential for normal growth and development from neonatal to adulthood. But in adulthood, at least with respect to glucose metabolism, the role of insulin is to control glucagon.