[science] Does insulin get on a diabetic's nerves?
Does insulin get on a diabetic's nerves?
John Timmer
http://arstechnica.com/journals/science.ars/2006/12/18/6322
December 18, 2006 @ 12:30PM
On more than one occasion, I've covered a science story where a number of results suggest that a clear understanding of something is tantalizingly close, but the complexity of the system or the lack of a few key results keep us from seeing the big picture. So it's a great pleasure to report on a situation where a few more pieces of data allow everything to fall into place. Building on a huge volume of seemingly unrelated data while adding some key bits themselves, scientists have generated a new understanding (free PDF) of the biology behind Type-I diabetes, the form caused by an immune assault on the body's own tissue.
The key observation that got the ball rolling came when the researchers noted that the islet cells of the pancreas, which produce insulin, are surrounded by a number of sensory neurons. They decided to check whether these neurons were involved with diabetes by working in a strain of mice, called NOD, which has been known since the 1980s to be prone to developing Type-I diabetes. Knowing that these were a specific type of sensory neurons, the researchers knew they could be killed by capsaicin, a compound found in chili peppers. Treating newborn NOD pups with capsaicin did, in fact, get rid of these pancreatic nerves. More remarkably, however, in many animals it also got rid of the immune cells that attack the pancreas and the resulting diabetic symptoms.
Because the NOD mice had been around for decades, researchers had been able to genetically map some of the locations of genes influencing their diabetic phenotype. The research group noted that one of these locations mapped right on top of a receptor expressed by these neurons. Checking its sequence, the researchers found two amino acid changes, and showed that the altered receptor had greatly reduced activity. Replacing this receptor in NOD mice with the normal version also blocked the diabetic phenotype, showing that the activity of these nerves was a critical part of the disease.
Although the key role of these sensory neurons was nailed down, these results leave the question of how the nerves are tied in to the autoimmune response in Type-I diabetes. Here the connection is a bit less clear, but the authors note that these neurons normally act to mediate a pain response via a neuropeptide known as substance P. Infusing the pancreas with substance P was sufficient to block both diabetic symptoms and a localized immune response. It's possible that the misregulation of the pain response triggered a distress or inflammatory signal in the islet cells, which in turn pulls in the immune cells.
Even without a definitive answer there, this work suggests that we might have assigned Type-I diabetes to the entirely wrong class of diseases: instead of being primarily autoimmune, its primary cause appears to be a poorly functioning nervous system. This sort of insight is likely to completely transform diabetes research. Better yet, the work shows that intervening via small molecules that target the nervous system (and we know of a lot of those) could be very effective in terms of restoring a body's natural production of insulin.
John Timmer
http://arstechnica.com/journals/science.ars/2006/12/18/6322
December 18, 2006 @ 12:30PM
On more than one occasion, I've covered a science story where a number of results suggest that a clear understanding of something is tantalizingly close, but the complexity of the system or the lack of a few key results keep us from seeing the big picture. So it's a great pleasure to report on a situation where a few more pieces of data allow everything to fall into place. Building on a huge volume of seemingly unrelated data while adding some key bits themselves, scientists have generated a new understanding (free PDF) of the biology behind Type-I diabetes, the form caused by an immune assault on the body's own tissue.
The key observation that got the ball rolling came when the researchers noted that the islet cells of the pancreas, which produce insulin, are surrounded by a number of sensory neurons. They decided to check whether these neurons were involved with diabetes by working in a strain of mice, called NOD, which has been known since the 1980s to be prone to developing Type-I diabetes. Knowing that these were a specific type of sensory neurons, the researchers knew they could be killed by capsaicin, a compound found in chili peppers. Treating newborn NOD pups with capsaicin did, in fact, get rid of these pancreatic nerves. More remarkably, however, in many animals it also got rid of the immune cells that attack the pancreas and the resulting diabetic symptoms.
Because the NOD mice had been around for decades, researchers had been able to genetically map some of the locations of genes influencing their diabetic phenotype. The research group noted that one of these locations mapped right on top of a receptor expressed by these neurons. Checking its sequence, the researchers found two amino acid changes, and showed that the altered receptor had greatly reduced activity. Replacing this receptor in NOD mice with the normal version also blocked the diabetic phenotype, showing that the activity of these nerves was a critical part of the disease.
Although the key role of these sensory neurons was nailed down, these results leave the question of how the nerves are tied in to the autoimmune response in Type-I diabetes. Here the connection is a bit less clear, but the authors note that these neurons normally act to mediate a pain response via a neuropeptide known as substance P. Infusing the pancreas with substance P was sufficient to block both diabetic symptoms and a localized immune response. It's possible that the misregulation of the pain response triggered a distress or inflammatory signal in the islet cells, which in turn pulls in the immune cells.
Even without a definitive answer there, this work suggests that we might have assigned Type-I diabetes to the entirely wrong class of diseases: instead of being primarily autoimmune, its primary cause appears to be a poorly functioning nervous system. This sort of insight is likely to completely transform diabetes research. Better yet, the work shows that intervening via small molecules that target the nervous system (and we know of a lot of those) could be very effective in terms of restoring a body's natural production of insulin.