Sherry, A. Dean, PhD
In vivo imaging of beta cell function with a zinc responsive contrast agent
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Insulin Action, Insulin Action\Metabolism, Other
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2012
Project End Date: June 30, 2016
Insulin, produced in the beta cells of the pancreas, maintains proper glucose levels by stimulating glucose uptake into other organs. For those who suffer from type 1 diabetes, insulin levels drop because the beta cells die. In response, the remaining beta cells individually begin to create more insulin, but they cannot fully compensate for the loss of other cells. For those who suffer from type 2 diabetes, the beta cells continue to produce insulin but its effect on organs is diminished. In response, the pancreas expands so beta cells can synthesize more insulin (prediabetes), but again, eventually they cannot compensate for the effects of the disease.
In both types of diabetes, the beta cells initially respond to the disease by increasing insulin production. In fact, the response of the beta cells occurs earlier than other symptoms of both type 1 and type 2 diabetes. This study will pioneer an MRI imaging technique that measures beta cell function. Such a technique will allow early detection of diabetes and provide a way to picture the progression of prediabetes and diabetes (for instance, in response to treatments). The research will use a novel contrast agent to image the effects of glucose on beta cell function in live pigs and to test whether or not the technique can be used to track the long-term effectiveness of implanted beta cells. This method, after FDA approval of the contrast agent, could be directly applied to humans suffering from either type 1 or type 2 diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
My research focuses on development of new types of imaging agents that may one day allow monitoring of the functional aspects of pancreatic beta cells in vivo. In particular, we develop responsive agents that “light up” or get bright in a normal MRI image of the pancreas. Currently, images of healthy and diabetic pancreas appear identical by MRI while the technology we are developing would reveal how well a pancreas is functioning, that is, an image of a healthy pancreas would appear brighter than that of a failing pancreas.
If sensitive enough, our method will allow early detection of diabetes and allow monitoring of beta cell function during various interventions. In addition, my research potentially provides a new tool for many other diabetes researchers. The MRI tools we are developing will potentially facilitate the scientific community’s basic understanding of insulin release from various anatomical regions of the pancreas during development of type 2 diabetes. It will allow researchers to see if their treatments are working in real time and will hopefully lead to new and improved treatments and even, one day, a cure for the disease.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
One of the difficulties for doctors and researchers that study diabetes is that there is no way to see by standard imaging methods whether the beta cells of a pancreas are working properly and whether all beta cells are functioning properly or only a few. The pancreas is the organ that produces, stores, and releases insulin into the bloodstream when blood sugar levels get too high. Currently, the best way to assess the health of the pancreas in an individual is to measure blood glucose (sugar) and blood insulin levels a few minutes after ingestion or injection of glucose. Unfortunately, many other biological processes in the body can also affect these blood levels making it difficult, sometimes, to know how healthy or diseased a patient’s pancreas is. Not only does this make healthcare difficult, but it also makes it hard to tell if a drug or treatment is working well.
My research project hopes to alleviate this problem. The goal of the project is to develop a new MRI technique that would allow a doctor or researcher to take a picture (an image) of the pancreas that shows which parts of the pancreas are working and how well. The technique will utilize a new contrast agent (a small molecule that is injected into the bloodstream as part of the MRI session) that “lights up” an MRI image of the pancreas, but only if the pancreas is functioning properly. If successful, this technique will help those with diabetes by giving their doctors a way to actually see how healthy their pancreas is. Along the same lines, doctors will then be able to see if your pancreas is responding to a certain treatment or not.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Like most people, just about everyone has a family member with type 2 diabetes so they understand how debilitating the disease can be. I first became interested in beta cell metabolism when I used the stable isotope 13C in combination with NMR to study how glucose is used by beta cells for energy and for insulin signaling. That led to my deeper understanding of beta cell metabolism and how we can use existing technologies to better understand how this changes during development of diabetes. I have more than 30 years experience in this area so I feel it is important to do whatever I can to better understand this disease. I am now committed to developing new imaging technologies to help diabetic patients knowing that one day this devastating disease could directly impact my life.
In what direction do you see the future of diabetes research going?
The biology of the disease is reasonably well understood. Now the biologists are turning to chemists, physicists, nanotechnology developers to help apply new technologies to allow imaging of biological processes in real time. This will speed development of new drugs to help combat this deadly disease.
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