Researchers uncover potential 'cure' for type 1 diabetes

January 26, 2011

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 .

"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.' "

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 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 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 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."

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13 comments

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epsi00
5 / 5 (6) Jan 26, 2011
the Nobel is waiting for this team.
Quantum_Conundrum
not rated yet Jan 26, 2011
the Nobel is waiting for this team.


Not if the Cold Fusion guys get it first...

I don't know though, seriously this is pretty big if it's true.

It too is on the same order as vaccines and refrigeration...hard not to give a Nobel for something like this, if it's true...
fmfbrestel
not rated yet Jan 26, 2011
yeah, lets hope continued trials are speedy and successful. I would also like to see what happens to the other effects of diabetes, specifically the poor circulation which shortens the life span of nearly all type 1 diabetics.
dogbert
not rated yet Jan 26, 2011
This is huge. If it leads to a cure for diabetes, its benefits are incalculable.

Most of our diseases are directly or indirectly associated with metabolic disorder (insulin resistance/diabetes). Vascular diseases, neuropathies, kidney diseases are all consequences of diabetes or insulin resistance.

I hope this research is accelerated. We really need an effective therapy for diabetes (or cure).
Trim
1 / 5 (1) Jan 26, 2011
Does it help those with type two diabetes who need insulin?
bfast
1 / 5 (1) Jan 26, 2011
As an insulin-requiring type 2 diabetic, I am dying to figure out why only type 1 diabetes is discussed here. Hopefully this will affect type 2s as well.
dogbert
not rated yet Jan 26, 2011
Type I diabetics do not produce insulin (or produce very little). Type II diabetics produce insulin, but the insulin no longer works to control blood sugar levels.

This alternate control mechanism, if it works, should work for both types, since it does not depend on insulin or insulin sensitivity.
omnivore
3 / 5 (2) Jan 27, 2011
Fascinating. But blood sugar rises with the ingestion of carbohydrate. Whether or not there is glucagon. How is dietary source blood glucose cleared? if not by insulin. It seems to me that a zero carb diet would also be necessary.
stealthc
2.5 / 5 (4) Jan 27, 2011
Excellent, now I can go out and eat that 40 lbs of chocolate in a week long binge without fear of dying of diabetes, hooray!
omnivore
5 / 5 (1) Jan 27, 2011
I am curious as to how ingested sugar is cleared (moved into cells) from the blood stream if not by insulin. The blocking of glucagon explains only the elimination of the blood sugar rise associated with glucagon's role of releasing glycogen from the liver. If you don't know the answer or are offended by the question just give me a 1 star ranking instead of answering as someone did above.
dtype1dancer
5 / 5 (1) Jan 27, 2011
I have many of the same questions as omnivore. I did find this article, however, which addresses the question a bit more. I can't post the URL here, but it's a Dallasnews.com article titled "UT Southwestern researchers on verge of possible diabetes breakthrough", and features Dr. Roger Unger.

The researchers only destroyed 90% of the mice's insulin-producing ability in the experiment mentioned in that article... which makes more sense to me; you'd think that some insulin would still be necessary.
omnivore
not rated yet Jan 27, 2011
Thanks for the lead dtype,
I could see how "partial" glucagon suppression,as mentioned in the Dallas article, between meals could be a useful tool. The success they had using leptin to control diabetes in mice was interesting too. I suspect diabetes treatment in the future will include modulating all three, insulin, glucagon and leptin. And. if science prevails over politics, low carbohydrate or ketogenic nutritional recommendations.
rynox
not rated yet Jan 27, 2011
I have many of the same questions as omnivore. I did find this article, however, which addresses the question a bit more. I can't post the URL here, but it's a Dallasnews.com article titled "UT Southwestern researchers on verge of possible diabetes breakthrough", and features Dr. Roger Unger.

The researchers only destroyed 90% of the mice's insulin-producing ability in the experiment mentioned in that article... which makes more sense to me; you'd think that some insulin would still be necessary.

Excellent article, thanks for the mention.

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