Harvard research scientists may have found a compound that will prolong the action of the body’s natural insulin, according to a report published in Nature. David Liu, professor of chemistry and chemical biology, and Alan Saghatelian, associate professor of chemistry and chemical biology, led their research group to discover a new compound that blocks the enzyme that breaks down insulin in mice. IDE (insulin degrading enzyme) was discovered sixty years ago, but finding a method to prolong its action was only a theory until now.
Compound Tested in Mice
The new compound was tested in mice who had become obese due to their diet; when the compound was given before meals, the mice had improved glucose tolerance. Glucose tolerance is a measure of how well an organism takes in and uses glucose. In diabetes, the body has a reduced ability to take glucose into the cells where it powers growth, activity, and many processes. Excess glucose in the blood that does not enter cells causes serious complications of diabetes, including nerve damage, kidney and eye disease, exhaustion, wasting, and heart disease. The IDE inhibitor also has impact on amylin (which delays stomach emptying) and glucagon (which stimulates the release of glucose stored in liver).
New Method to Test Potential Drugs More Quickly
The Harvard team refined its DNA-templated synthesis method over a decade and produced a library of 14,000 small chemical molecules. Short segments of DNA are linked to building blocks of molecules. The properties of DNA chemically bring the building blocks together, and the researchers then determine the composition of the molecules that are made, by finding the sequence of their attached DNA strands.
The new molecules are made quickly by this method, which allowed them to test many more compounds in a given time period than by previous methods.
“The creation of new technologies, and application of new technologies, is what gets me out of bed every day,” said Liu. The group’s discovery was enabled by their DNA templated synthesis method. Liu compared it to the natural selection process, where nature winnows down a population to the sturdiest and best adapted organisms over time. The DNA template method accelerates the process, compressing the time needed to complete research.
New Kind of Diabetes Treatment Ahead?
What could this new approach to diabetes treatment mean in clinical practice? Alan Carter, Pharm.D., chair of the Chronic Disease Alliance in Kansas (which grew out of the former Kansas Diabetes Action Council), suggests that a drug that has the potential to prolong the action of insulin could be most useful in treating type II (adult onset) diabetes. “Since insulin increases appetite, patients with insulin resistance or type II diabetes can find it much harder to control their diet.” Carter says it is not possible to forecast side effects of such targeted treatment, and adds, “An appetite stimulant effect could be a side effect of this kind of drug treatment.”
Slowing the Progression of Diabetes Is Critical
According to the American Diabetes Association (ADA), more than 8 percent of the adults and children in the U.S., or 25 million people, have diabetes. Although 18.8 million have been diagnosed, the remaining 7 million diabetics in this country suffer from diabetes but are not yet diagnosed. 79 million Americans have pre-diabetes, which is higher than normal blood glucose that has not reached the level in diabetes.
The ADA has found that diabetes raises the risk of many other diseases; it is the leading cause of kidney failure and new cases of blindness. During 2005 to 2008, among adults aged 20 years or older with self-reported diabetes, 67 percent had blood pressure greater than or equal to 140/90 mmHg, or used prescription medications for hypertension, and in 2004, heart disease was noted on 68 percent of diabetes-related death certificates among people aged 65 years or older.
The Centers for Disease Control and Prevention (CDC), graphically show that as recently as 1990, 2.5 percent of Americans were diagnosed with diabetes; by 2010, that percentage had grown to 6.95 percent.
This initial study proves it is possible to create a compound that blocks the breakdown of insulin, and suggests a new approach for diabetes drug development. Drug development may take years, and many stages of study, before a drug could be ready for testing on human beings.