Scientists unravel obesity surgery’s potent effect on diabetes

Imaging scans of a rat before (left) and after (right) gastric bypass surgery, showing increased glucose use by the intestine after the surgery.
Imaging scans of a rat before (left) and after (right) gastric bypass surgery, showing increased glucose use by the intestine after the surgery. –courtesy of Stylopoulos laboratory/Boston Children’s Hospital

For years, doctors have been intrigued and mystified by the remarkable power of weight loss surgery to treat type 2 diabetes. Stomach-shrinking gastric bypass surgery is typically used to treat extremely obese patients, but it has become clear that the intervention is more potent than doctors initially anticipated. Patients are often taken off of diabetes medicines before they have had significant weight loss — and before they even leave the hospital.

Researchers at Boston Children’s Hospital, curious what organ or bodily process could account for the body’s sudden improved regulation of blood sugar, put rats that had undergone a gastric bypass procedure into a PET scanner that tracks where sugar is in the body. In the scanner, one part of the rat’s body glowed with activity: the small intestine.


“What we found is it’s an energy guzzling organ after gastric bypass,’’ said Dr. Nicholas Stylopoulos, an obesity researcher at Children’s who led the work, published Thursday in the journal Science. The intestine “uses so much energy after gastric bypass, because it has to work harder.’’

The researchers studied the biomolecular changes in the intestine after surgery to try and pick apart what precise alterations could account for its new role as a hotspot for regulating blood sugar. What they found surprised them, because it isn’t typically found in the intestines of adults: a molecule that acts as a glucose transporter and ferries sugar out of the blood and into cells.

Understanding those changes in detail lays the groundwork for the search for effective diabetes therapies, Stylopoulos said. Now, scientists can examine whether it is possible to use a drug or other intervention to trigger the body to generate that transporter in the intestine.

That fits into the broader reason for figuring out how gastric bypass surgery works — not to expand the use of the surgery, but to help refine the search for less risky and invasive therapies that could have some of the same effects. For example, work published earlier this year found that transplanting the gut microbes from a mouse that has received gastric bypass surgery into another mouse will help spur weight loss.


Stylopoulos said the majority of the surgery’s effect on diabetes was due to the changes in the intestine, with about 36 percent of the effect accounted for by other changes such as weight loss.

What remains unclear, he said, is whether the same thing will be seen in people. The team is already planning to study PET scans of patients who have undergone gastric bypass surgery. It is also unclear to what extent the changes in the intestine might contribute to the weight loss.

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