Hostager, Bruce , PhD
SOCS7 regulation of insulin receptor signaling and pancreatic islet regeneration
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Insulin Action
Type of Grant: Basic Science
Project Start Date: January 1, 2010
Project End Date: December 31, 2012
The hormone insulin is crucial for the maintenance of normal blood glucose levels and cellular energy balance. Diabetes results from defects in insulin production by islet cells in the pancreas or from defective responses to insulin in body tissues. Normally, insulin also helps to regulate its own production, in part by regulating islet cell growth. Currently, molecular mechanisms controlling the body's response to insulin are only partially understood. A cellular protein known as SOCS7 appears to participate in the negative regulation of insulin responses. Consistent with this, insulin has more potent biological activities in mice genetically engineered to lack SOCS7. SOCS7-deficient mice also have a greater number of islet cells and are capable of greater insulin production than normal mice.
This suggests that the inhibition of SOCS7 protein function could have a two-fold benefit for diabetic patients: augmented insulin production and enhanced insulin activity. The proposed research will evaluate the potential for enhancing the regeneration and maintenance of endogenous or transplanted pancreatic islet cells through the inhibition of SOCC7 activity/expression. The molecular mechanisms by which SOCS7 regulates insulin responses and pancreatic islet cell growth will also be examined. Characterizing these mechanisms will be an important initial step in the rational design of novel SOCS7-targeted drugs that could be used to enhance islet regeneration and also improve insulin receptor signaling in other tissues including liver, muscle and brain.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Our research will explore a previously unknown regulatory mechanism that appears to modulate insulin receptor signaling as well as the growth and function of insulin-producing pancreatic islet cells. A key component of this regulatory mechanism is a protein known as SOCS7. At the present time, the physiological roles of SOCS7 are poorly defined. However, we have preliminary evidence showing that the inhibition of SOCS7 activity may enhance insulin receptor signaling and islet cell growth.
The goals of our research project are to confirm our preliminary observations and to better characterize the biochemical roles of SOCS7 in insulin receptor signaling and islet cell physiology. A more complete understanding of SOCS7 biology may lead to novel approaches for enhancing insulin receptor signaling as well as the regeneration, growth, and function of endogenous or transplanted insulin-producing cells in diabetic individuals. Future SOCS7-targeted therapies therefore have the potential to be useful in the treatment of both type I and type II diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Our research will lead to a more complete understanding of insulin receptor signaling and the physiological regulation of pancreatic islet cells. This knowledge will provide us with new biochemical targets for the design of drugs capable of enhancing insulin receptor signaling and the regeneration or growth of insulin-producing cells in the pancreas.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
For many years, the major aim of my research has been the characterization of biochemical pathways important for the regulation of human physiology. This research is important for advancing our understanding of molecular mechanisms critical for human health. Recently, I have begun research aimed at understanding the regulation of insulin production and the cellular responses to insulin. I have known many people afflicted with diabetes, and I understand how they could benefit from more effective treatments.
It would be rewarding for me to play a role in the development of such treatments. To date, much of my research has focused on biochemical mechanisms contributing to the regulation of the immune system. The award from the ADA will provide critical initial resources to allow me to expand my research and apply my training and experience to the characterization of mechanisms relevant to the prevention and treatment of diabetes.
In what direction do you see the future of diabetes research going?
I believe that significant advances in treating and preventing diabetes will stem from a greater understanding of the molecular mechanisms that regulate insulin receptor activity, the production of insulin, and the health of insulin-producing cells. It will be equally important to continue to define the biochemical chain of events leading to autoimmune destruction of insulin-producing cells in type I diabetes. Every protein or molecular interaction identified by current and future diabetes research represents a possible target for novel therapeutic agents capable of treating or preventing diabetes.
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