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.
"More than two million Canadians have diabetes. Diabetes is an epidemic in Canada and around the world that is growing at an alarming rate," says Dr. Philip M. Sherman, Scientific Director of the Institute of Nutrition, Metabolism and Diabetes at the Canadian Institutes of Health Research. "Since many people are undergoing bariatric surgery in an attempt to manage morbid obesity and the associated health problems, such as diabetes, it is critical that we understand how it works. The Canadian Institutes of Health Research is pleased to support Dr. Lam's work which increases our understanding and may offer a new approach to managing morbidity and premature mortality resulting from this illness."
Working with rats, Drs. Lam, Breen and colleagues designed and performed a series of elegant experiments on two different groups of rats: rats whose insulin-producing pancreatic islet cells were destroyed by toxins; and genetically-altered rats which experienced spontaneous autoimmune destruction of islet cells – similar to what happens in humans with type 1 diabetes.
Non-obese rats induced with uncontrolled diabetes or autoimmune type 1 diabetes had an experimental DJB surgery, a variation of the Roux-en-Y gastric bypass, the most common surgical method currently used to treat obese patients. Two days after DJB surgery, blood sugars were normal in the insulin-deficient diabetic rats.
Dr. Breen emphasized that further studies need to be undertaken to determine the long-term effects of this intervention in rodents, as well as to ensure the safety and efficacy of this procedure in humans.
Other researchers involved in the study include Brittany A. Rasmussen, Andrea Kokorovic and Grace W.C. Cheung from the Toronto General Research Institute and the Department of Physiology, University of Toronto; and Dr. Rennian Wang, from the Departments of Physiology and Pharmacology, University of Western Ontario.
The work was funded by the Canadian Institutes of Health Research, as well as a fellowship from the University Health Network and the Banting and Best Diabetes Centre, University of Toronto.
About Toronto General Hospital, University Health Network
Toronto General Hospital is a partner in the University Health Network, along with the Toronto Western Hospital, the Princess Margaret Hospital and the Toronto Rehabilitation Institute. These research hospitals are affiliated with the University of Toronto. The scope of research at Toronto General Hospital has made this institution a national and international resource for education and patient care, and a leader in diabetes, transplantation, cardiology, surgical innovation, infectious diseases and genomic medicine.
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