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Archive - 03 - 2011
March 31, 2011 (Max Planck Institute) Body weight influences the risk of developing diabetes: between 80 and 90 percent of patients with type 2 diabetes are overweight or obese. According to scientists at the Max Planck Institute for Neurological Research in Cologne and the Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), short ribonucleic acid molecules, known as micro-RNAs, appear to play an important role in this mechanism. The researchers discovered that the obese mice form increased levels of the regulatory RNA molecule miRNA-143. miRNA-143 inhibits the insulin-stimulated activation of the enzyme AKT. Without active AKT, insulin cannot unfold its blood-sugar-reducing effect and the blood sugar level is thrown out of kilter. This newly discovered mechanism could provide the starting point for the development of new drugs for the treatment of diabetes.The hormone insulin plays a key role in the regulation of blood sugar levels. If there is too much glucose in the blood, insulin opens the glucose transport channels in the cell membrane of muscles and fat cells. Glucose then reaches the bodys cells and the bloods sugar content sinks. Additionally, the insulin inhibits the production of new sugar in the liver. Type 2 diabetics are able to produce sufficient volumes of insulin; however, their cells are resistant to it - and the hormone is unable to fulfil its task. If untreated, this disease damages the blood vessels due to the raised blood sugar levels, which can lead to a heart attack or stroke.The molecular processes in the bodys cells responsible for the connection between body weight and diabetes are largely unknown. However, in all tissues that respond to insulin, Micro-RNAs can be found. The Cologne-based scientists working with Jens Brning, Director at the Max Planck Institute for Neurological Research and scientific coordinator of the Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases at the University of Cologne assume, therefore, that micro-RNAs may also play a role in type 2 diabetes. These short ribonucleic acid molecules can regulate the activity of genes and thus control protein production.The research group in Cologne has now discovered a new mechanism that leads to insulin resistance of the cells. Accordingly, obese mice form excess miRNA-143 in their livers. This RNA molecule silences genes that are responsible for the activation of the enzyme AKT and therefore inhibits insulin from activating AKT. AKT is important for glucose transport in the cell and for the inhibition of glucose synthesis in the liver. When the enzyme is inhibited, insulin fails to take effect and the blood sugar remains elevated, explains Jens Brning.For their research study, the researchers compared normal weight mice with obese mice with type 2 diabetes. They discovered that the diseased animals produce more than twice as much miRNA-143 in their livers than the normal ones. Moreover, the researchers found only a low concentration of the protein ORP8 in the obese mice which formed large quantities of miRNA-143. ORP8 stimulates insulin to activate AKT and therefore reduces the sugar content of the blood. If ORP8 is lacking, insulin is unable to take effect and the AKT remains inactive.The researchers do not yet know why obese mice form more miRNA-143 than their normal weight counterparts. If we succeed in explaining the signalling paths in the cell that lead to the production of miRNA-143, we will have a starting point for the development of new drugs for the treatment of type 2 diabetes, explains Jens Brning in reference to future research plans.
March 31, 2011 (Newswise) Physicians at The University of Texas Health Science Center at Houston (UTHealth) have begun enrollment for a pilot study on a promising surgical approach for the management of Type 2 diabetes.The procedure being tested is designed for adults who have Type 2 diabetes and who are overweight or obese but not morbidly obese. Millions of Americans have Type 2 diabetes and most are overweight.Involving surgery to the small intestine and stomach, the procedure, which is called an ileal transposition with sleeve gastrectomy, is intended to improve or resolve Type 2 diabetes. It will be performed at Memorial Hermann-Texas Medical Center.Type 2 diabetes is a serious health problem and can lead to blindness, limb amputation and heart disease. It is characterized by an elevated blood sugar level associated with the bodys inability to produce enough insulin and/or to use it properly.The researchers goal is to enhance the ability of a person with Type 2 diabetes to maintain a normal blood sugar level by moving a section of intestine closer to the stomach and reducing the size of the stomach.Currently, many with Type 2 diabetes must take medication on a daily basis to keep sugar levels in check.The surgical procedure has been associated with encouraging results in clinical research conducted abroad. If the procedure proves effective, it could allow some people with Type 2 diabetes to cut back or quit their medications.The objectives of the study include evaluating the safety of the procedure and determining its effectiveness compared to dietary and medical management of Type 2 diabetes.No one has compared this surgery directly to medical therapy in a randomized, prospective study like this, said Brad Snyder, M.D., the principal investigator of the study and an assistant professor of surgery at the UTHealth Medical School.The UTHealth doctors plan to treat 10 people with Type 2 diabetes surgically and 10 medically. Participants will be followed over a two-year period and their outcomes compared.If we can get patients into remission and off their medications, then we could open the door for people who want to pursue careers as firefighters, police officers and commercial pilots who may at times be limited by this disease, Snyder said.An estimated 26 million people in the United States have diabetes, reports the Centers for Disease Control and Prevention. In adults, Type 2 diabetes accounts for about 90 -95 percent of all diagnosed cases of diabetes. Also known as adult onset diabetes and non-insulin dependent diabetes mellitus, Type 2 diabetes is associated with older age, physical inactivity and certain ethnic groups.This disease takes a terrible toll on both patients and their families, said Erik Wilson, M.D., a study investigator and an associate professor of surgery at the UTHealth Medical School.The ileum is the final section of the small intestine and transposition means to change place. Human studies have shown that when you place the ileum closer to the stomach, food from the stomach enters the ileum quickly and hormones that help regulate diabetes are easily stimulated.In the procedure, surgeons remove a section of the ileum that is about 5 feet in length and reattach it. In addition, they remove about 80 percent of the stomach. It is a band-aid procedure that is performed through tiny incisions on the abdomen. As with surgical procedures, there is a risk of complication and the risk is anticipated to be in the 1 to 2 percent range.The procedure is similar to a treatment for morbid obesity - metabolic and bariatric surgery, which can involve surgery on the stomach and intestines. Research shows that oftentimes Type 2 diabetes improves or resolves in morbidly obese patient following gastric bypass surgery.Were not completely sure why people with morbid obesity and Type 2 diabetes experience this improvement following surgery, Snyder said. It could be a combination of the different metabolism of food, the improvement of insulin action or the improvement in insulin secretion, he said.This research will help us find some answers and could lead to future treatments, Snyder said.Metabolic and bariatric surgery is typically limited to people with a body mass index of 40 kg/m or more, or a BMI of 35 kg/m or more with an obesity-related condition in accordance with National Institutes of Health (NIH) parameters for bariatric surgery. BMI is a calculation based on height and weight.This pilot study for the surgical management of Type 2 diabetes is restricted to people with a body mass index (BMI) of 25 to 34 kg/m, which includes people who are overweight or obese. Participants must be between 21 and 55 years of age and being treated for Type 2 diabetes.The clinical trial team includes Philip Orlander, M.D., a professor of medicine and director of the Division of Endocrinology, Diabetes and Metabolism at the UTHealth Medical School, who medically treats people with Type 2 diabetes. When treating patients, Orlander often begins by recommending they lose weight through conventional means such as restricting their calories and exercising more, as well as taking commonly used medications for diabetes. If that fails and they are eligible for bariatric surgery, Orlander will recommend bariatric surgery as a way to control their Type 2 diabetes.The average person with Type 2 diabetes may be on 10 different medications to control their blood sugar, cholesterol and blood pressure, Orlander said. When we send people to bariatric surgery, a significant portion may be able to stop all of their diabetes, cholesterol and blood pressure medications.Frank Moody, M.D., a professor of surgery at the UTHealth Medical School with a longtime interest in the surgical treatment of digestive system diseases, is assisting the research team and said the study could shed light on hormones involved in the metabolic process. The team will be looking at the impact of surgery on the processing of sugars by the diabetic subjects with an expectation of fixing the break in their metabolism, Moody said.If successful, the next step could involve a large clinical trial, Snyder said. Our intention is to gather this primary data in a small group to show the safety and likely significance as well.Snyder, Wilson and Orlander are collaborating on the study with Kelly Wirfel, M.D., an assistant professor of medicine at the UTHealth Medical School. Snyder and Wilson are members of a UT Specialty Surgery Center called Minimally Invasive Surgeons of Texas (MIST) and are on the medical staff of Memorial Hermann-TMC. Wilson is the director of MIST, chief of Elective General Surgery for the UTHealth Medical School and medical director of Bariatric Surgery for Memorial Hermann-TMC.The study is titled A Surgical Approach to the Management of Type 2 Diabetes Mellitus in Patients with a BMI between 25-34 kg/m. The study was approved by the UTHealth Committee for the Protection of Human Subjects and is anticipated to take about three years to complete.
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