Field Notes

New Link Found Between Obesity and Diabetes

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

A drug that inhibits the enzyme MK2 eventually could be added to metformin to achieve better control over insulin and glucose levels than is possible with either drug alone, according to the researchers.

“MK2’s compatibility with metformin makes it a very exciting potential drug target,” says Ira Tabas, MD, PhD, the Richard J. Stock Professor and vice chair of research in the department of medicine and a professor of anatomy and cell biology in physiology and cellular biophysics, who led the study with Lale Ozcan, PhD, an 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,” Tabas explains. “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.”

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, Tabas and Ozcan, working with Columbia University Medical Center surgeons Marc Bessler, MD, and Beth Schrope, MD, PhD, also have recent unpublished data suggesting that MK2 is overactive in obese people, including those with prediabetes, but not in lean people.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 (Diabetes Genetics Replication and Meta-Analysis), a key component of the pathway that activates MK2 is associated with diabetes.

“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 prediabetes to full diabetes,” Tabas says.

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,” Tabas says. “If we can protect the pancreas’ beta cells from the stress of dealing with high glucose, we may be able to prevent or delay progression to full diabetes.”

— Source: Columbia University Medical Center

 

Microbiome Changed by Gluten Increases
Incidences of Type 1 Diabetes

Research has shown that the intestinal microbiome plays a large role in the development of type 1 diabetes. Now, researchers at Mayo Clinic have demonstrated that gluten in the diet may modify the intestinal microbiome, increasing incidences of type 1 diabetes. The research was published in PLOS ONE.

The researchers demonstrated that mice fed a gluten-free diet had a dramatically reduced incidence of type 1 diabetes. These mice were nonobese diabetic mice, or mice that grow to develop type 1 diabetes. The gluten-free diet worked to protect the mice against type 1 diabetes. When the researchers added gluten back into the diets of mice, it reversed the protective effect the gluten-free diet had provided. There also was a measurable impact of the gluten on the bacterial flora of the mice that might be one way in which gluten could affect the risk of diabetes.

“These changes suggest that the presence of gluten is directly responsible for the diabetes-creating effects of diet and determines the gut microflora,” says Govindarajan Rajagopalan, PhD, a Mayo Clinic immunologist and study author.

— Source: Mayo Clinic