Researcher reports intriguing diabetes breakthrough
By Jeffrey Weiss
http://www.JewishWorldReview.com | (MCT) A Dallas-based researcher says he's pulled off a medical first: successfully treating mice and rats dying of insulin-dependent diabetes without using insulin.
Dr. Roger Unger, chair of diabetes research at University of Texas Southwestern Medical School, is quick to warn that practical applications, if any, are years away. But the research team he headed used high levels of leptin, a substance naturally produced by fat cells, to somehow reverse the otherwise fatal effects of diabetes.
If the experiment is repeated in other labs, and then if leptin can be adapted to treat humans, it might offer the first alternate to the multiple insulin injections used by millions of people who have type 1 diabetes, Unger said.
How surprising was the result of the experiment?
"It would be like finding aliens landing in your backyard," Unger said.
It's not easy for diabetes to surprise Unger. He's been a top researcher for decades with a long list of honors from many major diabetes-related organizations. At 84, he's still someone that others in the field pay attention to.
His latest findings were published Monday in the Proceedings of the National Academy of Sciences. The paper, titled "Making insulin-deficient type 1 diabetic rodents thrive without insulin," will get plenty of attention, said Dr. Rohit N. Kulkarni, a researcher at the Joslin Diabetes Center and professor at Harvard Medical School who is also investigating the effects of leptin.
"I think it's very interesting and intriguing - with an emphasis on the latter," he said. "It's quite unexpected."
Leptin may blunt the short-term impact of Type 1 diabetes - the rapid weight loss and altered blood chemistry that make the untreated disease fatal. It may also help control the longer-term effects of the disease caused by abnormally high levels of sugar in the bloodstream.
But the results reported in this new paper offer almost as many questions as they do answers, Unger said. And he figures the initial reaction to the results from many other researchers will be negative, "just like mine was," he said.
Why is it such a surprise? Ever since 1921, when researchers first linked what is now known as type 1 diabetes to a lack of insulin, doctors have assumed that the only successful treatment replaced insulin, usually through multiple daily injections. This new experiment rejuvenated mice and rats without using insulin.
"There's not a human being who knows anything about diabetes who would have said they would get better without insulin," Unger said.
Specialized cells in the pancreas called beta cells respond to the level of sugar in the bloodstream by producing insulin. The hormone has at least two functions:
It acts like a key to a locking gas cap, letting many kinds of cells absorb sugar from the blood to use for fuel.
Insulin also sits on the opposite side of a biochemical teeter-totter from a hormone called glucagon. Glucagon tells liver cells to dump storage supplies of sugar into the bloodstream, providing more fuel as needed. At higher levels, it signals cells to convert amino acids and fats into fuel - basically telling the body to "burn" muscle and fat.
In Type 1 diabetes, which affects about a million people in the United States, the body's immune system mistakenly kills the beta cells - and the ability of the body to produce insulin.
Without insulin on the other side of the teeter-totter, excess glucagon over-triggers the consumption of muscle and fat, which produces the wasting and rapidly fatal symptoms associated with untreated type 1 diabetes, Unger said.
In the experiment reported in the new paper, Unger's team injected genetically modified viruses that infected the rodents' liver cells and turned them into leptin-producers.
In a matter of days, the wasting effects of excess glucagon stopped and blood sugar levels dropped near normal. After a few weeks, the leptin levels went down and the blood sugar levels went back up - but not nearly as high as for untreated mice. And the otherwise fatal high-glucagon symptoms never returned, even after almost a year.
A few scientists have thought that leptin was involved with the balance between insulin and glucagon and a few earlier experiments had used leptin along with insulin on rodents, but this is the first to show results without insulin, Unger said.
"Leptin seems to do everything that insulin does - and with a more prolonged effect," Unger said.
Among the many questions left for researchers:
But there are no promises that this work will ever produce practical treatments, Unger said. He has been disappointed before. In the 1970s, he worked with another protein called somatostatin that seemed to offer a new treatment for diabetes, but the effect was too short-lived.
The bottom line for Unger is that this research provides new choices for others searching for ways to treat type 1 diabetes.
"Over the years we all began to believe it was insulin or nothing," he said. "We hope this will open a door that was previously closed and inspire exploration for new and effective alternatives."
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© 2008, The Dallas Morning News. Distributed by McClatchy-Tribune Information Services