OHSU Researchers Locates Brain-Based Cause Of Type 2 Diabetes, Possible Method For Reversing Disease

02/24/11  Portland, Ore.

Researchers at the Oregon National Primate Research Center at Oregon Health & Science University have identified a cause of type 2 diabetes and a possible method for counteracting the obesity-linked disease. The research, which has been conducted with mice, will now be investigated in other animals. The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health, and the Fogarty International Center. Results are printed in this week's edition of the scientific journal Nature.

The research team, which includes scientists at OHSU, Harvard Medical School, and the University of Texas Southwestern Medical Center determined that a subset of brain cells, called POMC neurons, become defective in obese mice. The scientists also discovered that when defective, these specialized cells are unable to perform important functions, such as detecting and responding to high blood sugar (glucose) levels.

"In a healthy body, insulin, which is produced in the pancreas, helps regulate glucose levels and keeps them within healthy limits," explained Michael Cowley, Ph.D.,an associate scientist in the Division of Neuroscience at ONPRC. "Part of the regulation of glucose levels involves detection of glucose levels by the brain, and then regulation of many processes that keep blood glucose levels in a safe, healthy range. We have shown how one population of neurons, POMC neurons, detect blood glucose. We have also shown that when animals become obese, the POMC neurons no longer respond to glucose, and blood glucose levels rise."When the researchers genetically engineered the POMC neurons so that they did not sense glucose, animals were unable to properly control blood glucose levels. This demonstrated that the neurons have a role in sensing, and then regulating blood glucose levels. The researchers also discovered the basis of the defect in obese animals that caused these neurons to stop noticing glucose."

The research team then looked for methods to counteract the defective cells in obese mice. In doing so, they located a compound, which is derived from gardenia plants, called genipin, which was able to repair the POMC neurons' ability to sense and react to blood sugar levels.

Another important next step for the research team is to investigate their brain-based findings in other animals and humans to determine if these same conditions exist in the development of type 2 diabetes in other species. While these determinations have yet to be made, previous studies of obesity-related conditions in mice have translated to humans."We consider our findings to be very significant and we are very hopeful that they will result in a clearer understanding of type 2 diabetes and, more importantly, a treatment," said Cowley. "However, there is much more research to be done before we can determine how valuable these findings will be in the future."

About Type 2 DiabetesAccording to the Centers for Disease Control and Prevention, type 2 diabetes appears to account for 90 percent to 95 percent of all diagnosed cases of diabetes. Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Native Hawaiians or other Pacific Islanders are at particularly high risk for type 2 diabetes. Type 2 diabetes is increasingly being diagnosed in children and adolescents. The increase is likely linked to the significant rise in childhood obesity in the United StatesAbout ONPRCThe ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).