Experimental bariatric surgery controls blood sugar in rats with diabetes

For the first time, scientists at the Toronto General Hospital Research Institute have shown that an experimental bariatric surgery can lower blood sugar levels in rats with type 1 diabetes.

A team led by Dr. Tony Lam and Dr. Danna Breen, a post- doctoral fellow in the lab of Dr. Lam, used a rat model to study novel nutrient-sensing signals in the jejunum, located in the middle of the intestine. Dr. Lam and his team demonstrate that duodenal-jejunal bypass surgery activates novel nutrient-sensing signals in the jejunum and rapidly lowers blood sugar levels in non-obese rats with uncontrolled diabetes. DJB surgery is a type of bariatric surgery which excludes the duodenum and proximal jejunum, the first section of the small intestine, and instead redirects food into the distal jejunum, the middle to last section of the intestine. This latter section of the intestine, as demonstrated by Dr. Lam and his team, can sense glucose and signal to the brain to let the liver know that it must lower glucose production, leading to better control of blood sugar in the diabetic rats.

The study showed for the first time that a surgical intervention induces a rapid glucose-lowering effect in non-obese type 1 uncontrolled diabetic rats, independent of a reduction in food intake and body weight as well as changes in blood insulin levels.

The research was published in a paper entitled, "Jejunal nutrient sensing is required for duodenal-proximal jejunal bypass surgery to lower glucose levels in uncontrolled diabetes," in the May 20, 2012 on-line edition of the international journal Nature Medicine.

"We report that shortly after a meal, the influx of nutrients into the jejunum of DJB surgical diabetic rats activates novel sensing mechanisms to lower blood sugar levels. Importantly, this occurs in the presence of insulin-deficiency and is independent of weight loss," says Dr. Lam, who holds The John Kitson McIvor (1915 – 1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto. He is also Associate Director of Research at the Banting and Best Diabetes Centre at the University of Toronto.

Currently, patients with Type 1 diabetes lower their glucose through insulin injections (usually several times a day) and must regularly monitor blood glucose levels. High or uncontrolled glucose levels can result in damage to eyes, nerves and kidneys and increase the risk of heart attack, stroke, blindness, erectile dysfunction, foot problems and amputations. Many laboratories around the world are in a race to find alternative and effective ways in which to lower and better control glucose levels because of the severe complications which can result from high sugar levels.

Dr. Lam's laboratory is a world pioneer in exploring the role of the gut in regulating blood sugar. "The gut is an easier and therefore more promising therapeutic target in regulating blood sugar than the brain or liver, due to their potential side effects, " says Dr. Danna Breen, who is the lead author in the study. Dr. Breen adds that this type of surgery may potentially have therapeutic value in lowering glucose (sugar) levels in non-obese individuals with type 2 or 1 diabetes, but that many more years of future studies are required to determine whether this approach is effective and safe in humans who have diabetes.