potential cure of type 1 diabetes

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Researchers Uncover Potential Breakthrough Cure for 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, " says Dr.

Unger from UT Southwestern Medical Center....

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In this published study, UT Southerwestern Medical Center researchers

obtained normal blood sugars when they prevented the release of glucagon

from the liver and the release of insulin from the beta-cells.

The new findings suggest that Type 1 diabetes could be converted to an

asymptomatic, non-insulin-dependent disorder by eliminating the actions of a

specific hormone.

As we have learned from the thousands of diabetes studies and the coming and

going of cures for diabetes, there are many mechanisms and reactions

involved in the conversion of glucose to energy, so caution needs to be

taken with the results of this study, until it can be duplicated especially

in human subjects.

Scientists at UT Southwestern Medical Center studied the hormone glucagon,

which prevents low blood sugar in healthy people and causes high blood sugar

in people with Type 1 diabetes. When glucagon was suppressed in mice, the

hormone insulin became unimportant. Glucose tolerance returned to normal.

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.

Dr. Unger, professor of internal medicine and senior author of the study

stated that, " 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. " " 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.

" And if you don't have glucagon, then you don't need insulin. "

Dr. Young Lee, assistant professor of internal medicine at UT Southwestern

and lead author of the study, said the next step is to determine the

mechanism behind this result.

" Hopefully, these findings will someday help those with Type 1 diabetes, "

Dr. Lee said. " If we can find a way to block the actions of glucagon in

humans, then maybe we can minimize the need for insulin therapy. "

Dr. Unger said anything that reduces the need for injected insulin is a

positive.

" Matching the high insulin levels needed to reach glucagon cells with

insulin injections is possible only with amounts that are excessive for

other tissues, " he said. " Peripherally injected insulin cannot accurately

duplicate the normal process by which the body produces and distributes

insulin. If these latest findings were to work in humans, injected insulin

would no longer be necessary for people with Type 1 diabetes. "

Dr. May-Yun Wang, assistant professor of internal medicine at UT

Southwestern, and researchers from the Albert Einstein College of Medicine

also contributed to the work. The study was supported in part by the VA

North Texas Health Care System, the American Diabetes Association and the

National Institutes of Health.

Diabetes January 26, 2011 vol. 60 no. 2 391-397

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This article originally posted 01 February, 2011 and appeared in Medication

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