New brain pathways for understanding type 2 diabetes and obesity uncovered

Researchers at UT Southwestern Medical Center have identified neural pathways that increase understanding of how the brain regulates body weight, energy expenditure, and blood glucose levels — a discovery that can lead to new therapies for treating Type 2 diabetes and obesity.The study, published in Nature Neuroscience, found that melanocortin 4 receptors (MC4Rs) expressed by neurons that control the autonomic nervous system are key in regulating glucose metabolism and energy expenditure, said senior author Dr. Joel Elmquist, Director of the Division of Hypothalamic Research, and Professor of Internal Medicine, Pharmacology, and Psychiatry.”A number of previous studies have demonstrated that MC4Rs are key regulators of energy expenditure and glucose homeostasis, but the key neurons required to regulate these responses were unclear,” said Dr. Elmquist, who holds the Carl H. Westcott Distinguished Chair in Medical Research, and the Maclin Family Distinguished Professorship in Medical Science, in Honor of Dr. Roy A. Brinkley. “In the current study, we found that expression of these receptors by neurons that control the sympathetic nervous system, seem to be key regulators of metabolism. In particular, these cells regulate blood glucose levels and the ability of white fat to become ‘brown or beige’ fat.”Using mouse models, the team of researchers, including co-first authors Dr. Eric Berglund, Assistant Professor in the Advanced Imaging Research Center and Pharmacology, and Dr. Tiemin Liu, a postdoctoral research fellow in Internal Medicine, deleted MC4Rs in neurons controlling the sympathetic nervous system. …

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Salsalate lowers blood glucose in type 2 diabetes, study suggests

July 2, 2013 — Joslin scientists report that salsalate, a drug used to treat arthritis, lowers blood glucose and improves glycemic control in type 2 diabetes. These findings, which were published today by the Annals of Internal Medicine, provide additional evidence that salsalate may be an effective drug to treat type 2 diabetes.The scientists became interested in studying salsalate, an anti-inflammatory drug, after research conducted by Steven Shoelson, M.D., Ph.D., Head of the Section on Pathophysiology and Molecular Pharmacology and Professor of Medicine at Harvard Medical School, identified inflammation as a factor in the development of type 2 diabetes.Stage 1 of TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) evaluated varying doses of salsalate in 108 participants with type 2 diabetes for 14 weeks. This study was reported in the Annals of Internal Medicine in 2010. The current findings are based on Stage 2 of TINSAL-T2D, which evaluated 286 participants with type 2 diabetes for 48 weeks. The subjects’ blood glucose was inadequately controlled on current diabetes medications. Participants were randomized into salsalate and placebo groups.After 48 weeks of treatment, the mean hemoglobin A1c level (a measurement of average blood glucose control over the past six to twelve weeks) was 37 percent lower in the salsalate group compared to the placebo group. The decrease in fasting glucose concentration was 15 mg/dl greater in the salsalate group than the placebo group. Patients in the salsalate group required fewer additional diabetes medications to control their blood sugar than patients in the placebo group.”It’s exciting that salsalate is effective in lowering blood sugar,” says Allison Goldfine, M.D., lead author and Head of the Section of Clinical, Behavioral and Outcomes Research, and an Associate Professor of Medicine at Harvard Medical School. “Salsalate may have an important role in diabetes treatment and may also help us learn more about how inflammation contributes to the development of type 2 diabetes.”The salsalate group also showed improvements in markers associated with coronary risk: a 9 percent reduction in triglycerides and a 27 percent increase in adiponectin, a potentially cardioprotective protein from adipocytes. Uric acid, which is associated with cardiometabolic conditions and progression of renal disease, decreased 18 percent in the salsalate group. …

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Vegetarian diets associated with lower risk of death

June 3, 2013 — Vegetarian diets are associated with reduced death rates in a study of more than 70,000 Seventh-day Adventists with more favorable results for men than women, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication.The possible relationship between diet and mortality is an important area of study. Vegetarian diets have been associated with reductions in risk for several chronic diseases, including hypertension, metabolic syndrome, diabetes mellitus and ischemic heart disease (IHD), according to the study background.Michael J. Orlich, M.D., of Loma Linda University in California, and colleagues examined all-cause and cause-specific mortality in a group of 73,308 men and women Seventh-day Adventists. Researchers assessed dietary patients using a questionnaire that categorized study participants into five groups: nonvegetarian, semi-vegetarian, pesco-vegetarian (includes seafood), lacto-ovo-vegetarian (includes dairy and egg products) and vegan (excludes all animal products).The study notes that vegetarian groups tended to be older, more highly educated and more likely to be married, to drink less alcohol, to smoke less, to exercise more and to be thinner.”Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established,” the study notes.There were 2,570 deaths among the study participants during a mean (average) follow-up time of almost six years. The overall mortality rate was six deaths per 1,000 person years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs. nonvegetarians was 0.88, or 12 percent lower, according to the study results. The association also appears to be better for men with significant reduction in cardiovascular disease mortality and IHD death in vegetarians vs. nonvegetarians. In women, there were no significant reductions in these categories of mortality, the results indicate.”These results demonstrate an overall association of vegetarian dietary patterns with lower mortality compared with the nonvegetarian dietary pattern. …

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