Small Intestine Explains Diabetes 'Cure' After Gastric Bypass

Marlene Busko

July 26, 2013

"Reprogrammed" glucose uptake in the small intestine may explain why gastric-bypass surgery can sometimes result in the early resolution of type 2 diabetes, according to a new study in rats.

The report, by Nima Saeidi, PhD, and colleagues, at Boston Children's Hospital in Massachusetts, was published July 26 in Science.

Interestingly, patients with obesity-related diabetes who undergo Roux-en-Y gastric-bypass surgery for weight loss can often discontinue their antidiabetic medications before they are discharged from the hospital, the authors note. Investigators have hypothesized that the "cured" diabetes might be due to changes in hormones, fat, or muscle cells.

However, the current study revealed that in rat models of this surgery, the small intestine appeared to play a hitherto unrecognized role: it altered the way it processed glucose after the bypass surgery.

"Previously, we had not considered the intestine as a major glucose-utilizing organ, [but] we have found this process is exactly what happens after surgery," senior author Nicholas Stylopoulos, MD, said in a statement.

He and his colleagues performed a series of experiments in rats showing that after gastric-bypass surgery, the Roux limb, or part of the small intestine, was exposed to undigested nutrients.

This triggered glucose metabolism "reprogramming," such that the small intestine became a major organ for disposing glucose from the blood in the operated rats, compared with animals that underwent a "sham" procedure. The increase in intestinal glucose uptake in the rats undergoing bypass appeared to be largely due to an upregulation of the glucose transporter-1 (GLU-1) protein.

Future Drugs Might Let Patients "Bypass the Bypass"

If confirmed in other studies, this research suggests that pharmaceutical agents might be developed to target intestinal glucose metabolism, so that obese patients would not need to undergo bypass surgery, Dr. Saeidi and team say.

"Enhancing intestinal glucose uptake and use could offer an opportunity to regulate whole-body glucose disposal and improve glycemic control in type 2 diabetes," the authors write.

"Exploitation of the changes that occur in intestinal metabolism after [Roux-en-Y gastric bypass] could represent an approach to bypass the bypass—that is, to replace the gastric bypass by equally effective but less invasive treatments for obesity-related diabetes," they conclude.

The authors have disclosed no relevant financial relationships.

Science. 2013;341:406-410. Abstract

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