News & Research

    Albert Einstein College of Medicine, Bronx, New York

Insulin signaling and metabolic regulation

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Adipocytes, Insulin Action\Insulin Resistance, Islet Biology\Hormone Secretion and Exocytosis

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2009

Project End Date: June 30, 2013

Research Description

The inability of the body to respond to normal levels of insulin is known as insulin resistance. This physiologic state can both be a precursor and/or a consequence of diabetes resulting in reduced clearance of glucose from the blood due to an impairment in glucose transport in muscle and adipose tissues. Our laboratory is focused on understanding the molecular mechanisms responsible for the normal insulin stimulation of glucose uptake and to identify the steps that are dysfunctional in states of insulin resistance and diabetes.

Our laboratory utilizes various experimental approaches ranging from protein chemistry and structural biology to cell and molecular biological in model cell lines and physiologically in transgenic and knockout mice. In addition, The Albert Einstein College of Medicine offers additional state-of-the-art facilities that include non-invasive imaging, fluorescent and electron microscopy, metabolomic and animal integrative physiology cores as integral parts of the Diabetes Center that provide an outstanding training environment for research fellows.

Thus, entering postdoctoral fellows will have the opportunity to investigate several fundamental problems associated with insulin action at the physiological, cell biological and molecular levels. This broad training environment couple with various journal clubs, workshops and individual interactions will provide sufficient flexibility for the fellow to develop into an independent research investigator. Based upon a mutually agreed upon project, the fellow will be provided with ample research space, equipment and supplies. Subsequently, the fellow will be exposed to personnel management through the direct supervision of a research technician and/or collaborative work with graduate students.

Reseacher Profile

Mentor: Jeffrey Pessin, PhD   Postdoctoral Fellow: Daorong Feng

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 project serves two primary goals. The first one is to train the next generation of creative scientists who can apply their knowledge and efforts to understanding the molecular defects and complications associated with diabetes. Ultimately, it will take a concerted effort from numerous investigators and others individuals to understand and eventually develop the best therapies and/or cure for diabetes. As such, it is critical that we continually train and bring to this field new outstanding individuals working in this field. Thus the first goal is use these Mentor-based fellowship funds to foster the training of the next generation of diabetes focused scientists.

In particular, the current Fellow (Dr. Daorong Feng) is examining the molecular basis of insulin resistance that occurs during high fat diet induced obesity. She is examining the adipocyte signals that activate macrophages resulting in the induction of the pro-inflammatory response and subsequent adipocyte hyperplasia (increased number of adipocytes). In this process, adipocytes undergo a specific type of adipocyte program of cell death (necrosis) that releases factors that activate the innate immune system partictular macrophages. She is working on establishing the mechanisms responsible for this negative signaling pathway and developing strategies to alter this to an anti-inflammation response that will result in a reduction in adipocyte number (decreased obesity) and increased insulin sensitivity.

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

Currently, we know that in type 2 diabetes peripheral tissue insulin resistance (sometimes referred to as pre-diabetes) is the initiating event that eventually leads to the development of diabetes. The large increase in individuals with insulin resistance and diabetes parallels the increase incidence of obesity. This is consistent with obesity inducing states of insulin resistance in both humans and animal models. Thus, if we can reduce obesity we will markedly reduce the number of type 2 diabetic patients. The goals of our project are to specifically address these two issues, that is, what is the mechanisms accounting for insulin resistance and its relationship to the increase in obesity. Recent studies have shown that obesity is associated with a pro-inflammatory state in which a particular pro-inflammatory cell type invades adipose tissue.

Blockade of this pro-inflammation process protects against the development of insulin resistance but does not prevent the adipocyte tissue expansion. Our data suggests that caloric excess actually results in adipocyte programmed cell s death that in turn releases pro-inflammatory and differentiation factors that first initiate the pro-inflammatory response and subsequently lead to adipose tissue expansion (hyperplasia) resulting in obesity. Thus, by understanding the mechanisms of how caloric excess actually kills adipocytes, we will be able to generate new therapies that will be effective both against weight gain and insulin resistance.

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

While I was pregnant I developed gestational diabetes and this made me concerned not only for my own health but that for my unborn child. I realized that despite being normal healthy, diabetes could take a toll on my child and myself, now and in the future. Working in a diabetes research oriented laboratory is providing me the opportunity to be part of an important effort to prevent and/or cure diabetes that reduces the quality and quantity of life of so many people.

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

Great strides have been made in the past several years and in our understanding of both type 1 and type 2 diabetes. In the area of type 2, we are now establishing a fundamental understanding of the process responsible for insulin resistance, the primary inducing for the subsequent development of type 2 diabetes. With more detailed understanding of this mechanism, targeted therapies should follow in reasonably short time frame. Although these approaches are very exciting, the more studies are also needed to understand those individuals that are genetically susceptible to this inflammatory process versus those individuals whom are not. Since these events are environmentally influenced, more effort needs to be placed on epigenetic analyses in both humans and animal models.