Experimental Bariatric Surgery Controls Blood Sugar in Rodents With Diabetes Via Novel Sensing Signa

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 nutrientsensing signals in the jejunum located in the middle of the intestine Dr Lam and his team demonstrate that duodenaljejunal bypass surgery activates novel nutrientsensing signals in the jejunum and rapidly lowers blood sugar levels in nonobese 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 glucoselowering effect in nonobese 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 quotJejunal nutrient sensing is required for duodenalproximal jejunal bypass surgery to lower glucose levels in uncontrolled diabetesquot in the May 20 2012 online edition of the international journal Nature Medicine
quotWe 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 insulindeficiency and is independent of weight lossquot 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 Lams laboratory is a world pioneer in exploring the role of the gut in regulating blood sugar quotThe 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 quot 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 nonobese 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
In healthy individuals insulin is a hormone whose primary role is to regulate blood sugar It is produced by cells located on the pancreas in response to sugar intake and it acts to bring blood sugar to appropriate levels allowing the body to have the energy it needs to function properly In persons with type 1 diabetes the pancreas does not produce insulin resulting in elevated blood sugar levels due to lack of insulin which cannot signal to the liver to reduce sugar production People with type 1 diabetes need to take daily insulin shots and carefully monitor their blood sugar levels
quotIf new medicines or surgical interventions can be developed that stimulate this sensing mechanism in the gut we may have an effective and alternative way of slowing down the bodys production of sugar thereby lowering blood sugar levels in diabetesquot says Dr Lam who is also an Associate Professor of Medicine and Physiology at the University of Toronto Other ongoing studies of Dr Lams lab reveal novel molecular targets in the gut that effectively lower blood sugar in obesity and type 2 diabetes
Studies reported in the New England Journal of Medicine this year have challenged medical therapy as the prevailing method of treating patients with type 2 diabetes Two studies reported that bariatric surgery induced remission in severely obese patients with type 2 diabetes and was associated with significant improvement in metabolic control over and above medical therapy both conventional and intensive An accompanying April 26 2012 editorial by Drs Zimmet and Alberti states that quotsurgeons may now be able to claim greater success in achieving metabolic controlquot in these patients although longterm studies with greater numbers of patients still need to be completed No studies have yet reported on surgical interventions as treatments for patients with type 1 diabetes
quotMore than two million Canadians have diabetes Diabetes is an epidemic in Canada and around the world that is growing at an alarming ratequot says Dr Philip M Sherman Scientific Director of the Institute of Nutrition Metabolism and Diabetes at the Canadian Institutes of Health Research quotSince 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 Lams work which increases our understanding and may offer a new approach to managing morbidity and premature mortality resulting from this illnessquot
Working with rats Drs Lam Breen and colleagues designed and performed a series of elegant experiments on two different groups of rats rats whose insulinproducing pancreatic islet cells were destroyed by toxins and geneticallyaltered rats which experienced spontaneous autoimmune destruction of islet cells similar to what happens in humans with type 1 diabetes
Nonobese rats induced with uncontrolled diabetes or autoimmune type 1 diabetes had an experimental DJB surgery a variation of the RouxenY gastric bypass the most common surgical method currently used to treat obese patients Two days after DJB surgery blood sugars were normal in the insulindeficient diabetic rats
Dr Breen emphasized that further studies need to be undertaken to determine the longterm 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 WC 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

Date : 21 May, 2012
Reference : http://www.sciencedaily.com/releases/2012/05/120520133517.htm

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