Evaluating Pancreatic Neuromodulation for Prediabetes and Diabetes
Abstract
Diabetes is a devastating disease for individual patients, family members, and the larger community. In the US, one in nine people have diabetes and 84 million people are pre-diabetic, but incidence is even higher in at-risk groups including Veterans. It’s well known that the risk of diabetes increases as body weight rises, but it is not just the two-thirds of the US population who are overweight or obese that are at high risk. It is also more prevalent in people who have had head injuries, severe stress, or exposure to certain chemical, factors that contribute to the very high levels of diabetes seen in Veterans and Service families. One in four Veterans has diabetes. Preventing and treating diabetes is difficult. A healthy diet and exercise regimen that reduces weight decreases the risk of diabetes, but these changes are difficult to maintain over time. For people with diabetes, many studies show that the long-term consequences can be reduced with insulin treatments to keep glucose levels close to normal. But these targets can be very difficult to achieve, especially in those who are above ideal weight. And with intensive treatment, there is a greater risk of low blood glucose that can itself be harmful. So a broader range and better therapies to lower diabetes risk and treat diabetes is clearly needed. The studies proposed here will form a foundation for new therapies to prevent and treat diabetes. The aim of our studies is to identify the pancreatic nerves that are critical to glucose control, and how and when they are disrupted by over-eating. Diabetes is commonly thought of as a disease of the insulin-producing cells in the pancreas, but these cells receive signals from a dense network of nerves. It is now clear that neural signals to the pancreas play crucial roles in controlling the level of blood glucose. Many studies in animals and humans have shown that neural signals can regulate the release of pancreatic hormones, including insulin, to regulate blood glucose. However, the structure of the pancreatic nerves is abnormal in diabetes and their function is also impaired. In addition, the nerve activity to organs like the pancreas is disrupted in people at high risk of diabetes, even before they develop the disease. Therefore, activating pancreatic nerves could be used to normalize blood glucose by increasing insulin release. There have been a few clinical studies using nerve stimulation, already approved for conditions such as epilepsy, to regulate blood glucose, but they have been disappointing. This is because we do not yet know which nerves are the best targets, the optimum intervention (stimulating or blocking), and when these treatments are most effective. Our studies will address these questions. Pancreatic nerves are likely to be key to glucose regulation. We have developed new improved methods to examine the structure of pancreatic nerves that allows us to see their three-dimensional architecture and interactions with insulin-producing pancreatic beta cells. With this technique, we see that overeating leads to dramatic changes in pancreatic nerves. Next, by using a novel technology, we can remotely switch on or switch off just the nerves to the pancreas and rapidly and dramatically alter blood glucose, showing that these nerves play a key role in blood glucose control. Additionally, we have shown that with overeating, these nerves no longer function normally, suggesting a role in disease. This proposal will establish the connections of specific sets of pancreatic nerves to hormone-producing cells, how they control blood glucose, and determine the effects of a high fat diet on the connections and function. We will do so by examining the 3D architecture of the nerves, their roles in glucose control, and determining how and when the structure and functions are changed by overeating. In this proposal, we will be using a novel combination of innovative techniques that enable precis
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010345
Entities
People
- Sarah Stanley
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army