It has been known for some years that naturally occurring mutations in the gene which controls myostatin results in double-muscling in cattle, dogs and even humans. Many in the body building community believe that blocking myostatin is a shortcut to the Arnold Schwarzenegger body.

The flipside is that producing too much myostatin has been linked with muscle wasting conditions such as HIV-AIDS, starvation and now, Type 2 diabetes.

Hittel believes this may be due to a pre-diabetic condition known as insulin resistance that "tricks" the muscles into thinking the body is starving despite the fact that blood sugar levels are skyrocketing.

"When that happens, the body reverses muscle production using myostatin," says Hittel. "This is particularly worrisome because losing muscle mass further erodes your ability to control your blood sugar with exercise."

One of the tell-tale signs of the transition between insulin resistance and full-blown Type 2 diabetes is a loss of muscle mass.

"Losing muscle mass makes sense from an evolutionary perspective since having large muscles during famine puts you at a serious risk for starvation," explains Hittel. "Unfortunately, this survival mechanism has left us ill-equipped to deal with a Western lifestyle-lots of calories, little exercise-and it has laid the groundwork for the current epidemic of Type 2 diabetes."

"The goal of my research is to understand how obesity, diet and exercise influence our metabolism and interact with our genome. This research sheds some light on an important part of the puzzle."

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That pathway, the interleukin 12 (IL12) pathway, governs cell receptors involved in the development of Crohn's disease. Hakonarson added that the IL12 pathway might be more correctly referred to as the IL12/IL23 pathway, since IL12 receptor signaling converges with signaling on another receptor, IL23. Previous work by other researchers had shown that monoclonal antibodies that block the IL12 or IL23 receptor show some clinical success in treating Crohn's disease.

"As we better understand the gene pathways operating in Crohn's disease, we are uncovering more potential targets for effective drug treatments," said pediatric gastroenterologist Robert Baldassano, M.D., a study co-author and the director of the Center for Pediatric Inflammatory Bowel Disease at Children's Hospital. He added that developing targeted therapies based on gene pathways might allow doctors to tailor treatments to a patient's genetic profile.

The study team performed the initial analysis in DNA from 1,758 patients with Crohn's disease and 1,480 control subjects, all of European ancestry. They repeated the study in three additional groups, of both European and African American ancestry, and were able to replicate their results. Their study was the first to use a pathway-based approach to analyze GWA, without deciding beforehand to concentrate on a specific pathway.

For children and adults with Crohn's disease, who suffer the debilitating effects of chronic gastrointestinal inflammation, the emerging gene data may open the doors to more effective treatments. "Blocking cell receptors at some points on a biological pathway may produce clinical improvements, but with side effects to the immune system," said Baldassano. "If we can block other molecules further downstream on a pathway, we may achieve better treatments that may be more specific to an individual patient, with fewer side effects."

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