About Careers Internship MedBlog Contact us
Medindia LOGIN REGISTER
Advertisement

Researchers Identify New Link Between Obesity and Diabetes

by Kathy Jones on November 24, 2013 at 7:23 PM
 Researchers Identify New Link Between Obesity and Diabetes

Mouse studies done by researchers at Columbia University Medical Center reveal that a single overactive enzyme worsens the two core defects of diabetes—impaired insulin sensitivity and overproduction of glucose. This suggests that a drug targeting the enzyme could help correct both defects at once. The findings were published today in the online edition of Cell Metabolism.

A drug that inhibits the enzyme, MK2, eventually could be added to metformin—the current first-line treatment for type 2 diabetes—to achieve better control over insulin and glucose levels than is possible with either drug alone, said the researchers.

Advertisement

"MK2's compatibility with metformin makes it a very exciting potential drug target," said Ira Tabas, MD, PhD, Richard J. Stock Professor and Vice Chair of Research in the Department of Medicine and professor of anatomy & cell biology (in physiology and cellular biophysics), who led the study with Lale Ozcan, PhD, associate research scientist.

"The one clear leader among drugs currently available for type 2 diabetes is metformin, which does a pretty good job of attacking both problems. But because metformin is often not enough, we need drugs that can be added to metformin—or used in patients who cannot tolerate metformin," Dr. Tabas said. "If you take an obese, diabetic mouse and give it metformin, you get a partial improvement. If you give it an MK2-inhibitor, you also get a partial improvement. However, if you give both, the benefit is additive, which is consistent with our data that metformin and MK2 work through different biochemical pathways."
Advertisement

The researchers' earlier findings, on MK2's effects on glucose, were published last year in the same journal.

Though both papers report the biochemical details of how MK2 works in mice, Drs. Tabas and Ozcan, working with CUMC surgeons Marc Bessler, MD, and Beth Schrope, MD, PhD, also have recent unpublished data suggesting that MK2 is overactive in obese people, including those with pre-diabetes, but not in lean people. Moreover, the MK2 pathway is active in human liver cells, and, according to a large human genetic study called DIAGRAM, a key component of the pathway that activates MK2 is associated with diabetes.

About 25.8 million people in the U.S. and 347 people worldwide have diabetes (mostly type 2). According to the Centers for Disease Control and Prevention, each year, about 6 percent of people with pre-diabetes develop type 2 diabetes; unless they make lifestyle changes, about 15 to 30 percent will develop diabetes within five years. "In addition to improving insulin sensitivity and glucose levels, our data suggest to us that a drug that inhibits MK2 could prevent the progression of pre-diabetes to full diabetes," Dr. Tabas said.

Such a drug could protect the cells that produce insulin. "As the disease progresses, the insulin-producing cells have to put out more and more insulin to deal with the ever-increasing amounts of glucose in the bloodstream. Eventually, they burn out and the patient must use insulin," Dr. Tabas said. "If we can protect the pancreas's beta cells from the stress of dealing with high glucose, we may be able to prevent or delay progression to full diabetes."

Drs. Tabas and Ozcan are planning to test this hypothesis with pre-diabetic mice.

Inhibiting MK2 also reduces cholesterol

Unpublished data from Drs. Tabas and Ozcan also suggest that MK2 inhibitors may not carry the cardiovascular risks associated with several newer diabetes drugs. Because of these risks, the FDA will not approve a new diabetes drug unless it has been found to be safe in large clinical trials designed to detect cardiovascular risk.

The Columbia researchers' mouse studies show that MK2 inhibition reduces cholesterol, and other researchers have found that MK2 deficiency in mice protects against atherosclerosis. "A drug that inhibits MK2 may not just be heart-safe, but may actually be cardio-protective," Dr. Tabas said.

He and Dr. Ozcan have created a company to develop compounds able to inhibit MK2.

"As with all drug development, it's a long shot, but we think MK2 is less of a long shot than most."

Drs. Tabas' and Ozcan's paper is titled, "Activation of Calcium/Calmodulin-Dependent Protein Kinase II in Obesity Mediates Suppression of Hepatic Insulin Signaling."



Source: Eurekalert
Font : A-A+

Advertisement

Advertisement
Advertisement

Recommended Readings

Latest Obesity News

Pathbreaking Anti-Obesity Drug KDS2010 Helps Burn Fat Without Diet Restrictions
KDS2010 drug was found to regulate astrocytes in brain which enhances fat metabolism resulting in weight loss without the need for dietary restrictions.
Inflammation Impacts Weight Loss Post Bariatric Surgery
In obese patients undergoing weight-loss surgery, higher blood levels of inflammation are associated with poor weight loss post-surgery.
Coconut Oil Supplements Linked to Fuel Obesity
Coconut oil supplements over a long period of time may have a major impact on the metabolic changes in diet that can lead to obesity.
Anti-Obesity Drug Liraglutide Enhances Associative Learning
Intake of anti-obesity drug liraglutide, resulted in better brain activity and in-turn finer associative learning in obese individuals.
Nature's Anti-obesity Secret from China
Anti-obesity potential of a tropical plant emerges as a promising solution to address the global surge in obesity-related lifestyle diseases.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close
MediBotMediBot
Greetings! How can I assist you?MediBot
×

Researchers Identify New Link Between Obesity and Diabetes Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests