News & Research

    The J. David Gladstone Institutes, San Francisco, California

Progranulin, inflammation, and diabetes

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Complications, Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Integrated Physiology, Integrated Physiology\Insulin Resistance, Obesity, Obesity\Pathogenesis

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2012

Project End Date: June 30, 2016

Research Description

Recent studies have highlighted the role of inflammation in developing obesity-associated diabetes. A fat protein called progranulin was recently identified as a major factor in promoting diabetes. Additionally, in models of inflammatory diseases such as arthritis and infection, progranulin has been shown to block inflammation and improve the disease symptoms. In addition to their many years of work on obesity and diabetes, the Farese laboratory also coincidently studies progranulin. These studies to date have focused on progranulin and its role in dementia, but the Farese laboratory and others have also shown that progranulin blocks inflammation in the brain and in the body. There are many unanswered questions about how progranulin causes obesity or diabetes. Does progranulin block inflammation to improve the disease outcome or does it propagate inflammation to worsen the disease? The Farese group has expertise and research tools to investigate this topic.

With these and a track record of success studying obesity and diabetes, the postdoctoral fellow is uniquely suited to successfully address questions concerning: 1) how progranulin action in inflammatory cells leads to the development of diabetes, and 2) the basis of how progranulin helps high density lipoprotein (the good cholesterol) block inflammation. Understanding how progranulin blocks, or promotes, inflammation may advance potential therapies for heart disease and diabetes.

Research Profile

Mentor: Robert V. Farese, Jr., PhD
Postdoctoral Fellow: Thi Nguyen, PhD

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Recent studies have highlighted the role of inflammation in developing obesity-associated diabetes. A protein called progranulin, which is shown to block inflammation, was recently identified as a major factor in promoting diabetes. However, it is still unknown whether progranulin blocks inflammation to improve the disease outcome or if it propagates inflammation to worsen the disease. Our projects address questions concerning: 1) how progranulin action in inflammatory cells leads to the development of diabetes, and 2) the basis of how progranulin helps high density lipoprotein (the good cholesterol) block inflammation. Understanding how progranulin blocks, or promotes, inflammation may advance potential therapies for heart disease and diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Beyond diet and exercise it is important to understand the biology that underlies the development of type 2 diabetes. More specifically, why do some people with obesity get diabetes but others do not? Diabetes is closely linked with obesity and inflammation. Our work is focused on understanding how proteins and cells types involved in obesity-related inflammation can lead to the development of diabetes. We hope to use our experience and knowledge of progranulin biology to move our discoveries toward knowledge that may result in new therapies.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

Mentor: I have cared for many patients with diabetes and obesity and witnessed firsthand the challenges of living with this disease. Those affected frequently have the deck stacked against them and are unable to combat their problems with simple lifestyle changes. These people need new and safe therapies to lower body weight, decrease fat-related inflammation, and be free of diabetes. Currently, while we have therapies that reduce blood sugar, we have little to offer for reducing body weight safely and effectively. This approach is crucial if we are to improve the health of these individuals.

Fellow: Obesity and diabetes are increasing at an alarming rate in the United States, especially in children. I am strongly motivated to focus on diabetes-oriented research to contribute knowledge that may improve the health of future generations. This award provides me the opportunity to pursue this mission. I hope that our research discoveries may someday lead to new and more effective treatments for diabetes.

In what direction do you see the future of diabetes research going?

There are two main directions. First, research for improving insulin production by beta cells is important. Insulin is used to treat both type 1 and type 2 diabetes. The use of induced pluripotent stem cells to regenerate beta cells in a patient-specific manner is a particularly exciting avenue of research. The second thrust of research is aimed at limiting obesity, through one of many approaches: behavioral modifications, appetite suppressants, agents that limit energy assimilation, or those that increase energy expenditure. Additionally, preventing the inflammation associated consequences of obesity could be greatly beneficial. Research is crucial in all of these areas, from the basic biochemical and cellular processes to genetics to the complex physiological mechanisms that underlie the metabolic derangements, to make progress toward alleviating suffering from diabetes.