News & Research

    Beth Israel Deaconess Medical Center, Boston, Massachusetts

Mechanisms of insulin and leptin action and pathogenesis of obesity and type 2 diabetes

General Research Subject: Obesity

Focus: Integrated Physiology\Insulin Resistance, Insulin Action\Transgenic Models, Insulin Action\Metabolism

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2009

Project End Date: June 30, 2013

Research Description

A major cause of type 2 diabetes is failure of insulin to stimulate the uptake and metabolism of sugar.  This failure also contributes to problems associated with obesity.  The overall goals of the laboratory are to determine 1) the mechanisms within cells that impair insulin action in diabetes and obesity and 2) the molecular events and signals in cells that lead to obesity.  Complementary approaches include studying metabolism and signaling relays in whole mice, creating mice with increased or decreased expression of specific genes in certain tissues, using non-infectious viruses as carriers of genes into cells, assessing gene expression, purifying proteins, and cloning novel proteins. 

Major research areas include: 1) Determining how a protein which carries vitamin A in the blood and which we found is linked to insulin resistance, diabetes and cardiovascular risk may cause these problems.  2) Discovering novel substances released by fat cells that alter insulin action in other tissues.  3)  Determining the circuits in the brain responsible for the actions of a key enzyme that usually blocks signaling from insulin and leptin.  Lack of this enzyme in the brain causes leanness and insulin sensitivity.  4) Discovering mechanisms by which hormones and nutrients regulate another key enzyme, AMP-activated protein kinase. 

The lab investigates modifications of this enzyme complex in altered physiologic states to determine approaches to modify its activity for therapeutic benefit. Ideally, these projects will lead to new medications to prevent or treat obesity and Type 2 diabetes.

Reseacher Profile

Mentor: Barbara Kahn, MD   Postdoctoral Fellow: Yossi Dagon, PhD

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

The overall goals of my laboratory are to determine 1) the mechanisms within cells that impair insulin action in type 2 diabetes and obesity and 2) the molecular events and signals in cells that lead to obesity.  Complementary approaches include studying metabolism and signaling relays in whole mice, creating mice with increased or decreased expression of specific genes in certain tissues, using non-infectious viruses as carriers of genes into cells, assessing gene expression, purifying proteins, and cloning novel proteins.  When possible, we extend our studies to human tissues. Some of our discoveries have led to new therapeutic targets to prevent or ameliorate obesity, insulin resistance, and Type 2 diabetes.

Studies in my lab will lead to a better understanding the causes of type 2 diabetes and the molecular links between obesity and type 2 diabetes.  This could lead to new treatments and to new strategies for a cure.

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

A major cause of type 2 diabetes is failure of insulin to stimulate the uptake and metabolism of sugar.  This failure also contributes to problems associated with obesity.  Major research areas in my lab include: 1) Determining how a protein which carries vitamin A in the blood and which we found is linked to insulin resistance, diabetes and cardiovascular risk may cause these problems.  2) Discovering novel substances released by fat cells that alter insulin action in other tissues.  3)  Determining the circuits in the brain responsible for the actions of a key enzyme that usually blocks signaling from insulin and leptin.  Lack of this enzyme in the brain causes leanness and insulin sensitivity.  4) Discovering mechanisms by which hormones and nutrients regulate another key enzyme, AMP-activated protein kinase.  The lab investigates modifications of this enzyme complex in altered physiologic states to determine approaches that could lead to new therapeutic approaches. Ideally, these projects will lead to new medications to prevent or treat obesity and Type 2 diabetes.

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

I am committed to making discoveries that will improve the lives of people with diabetes and eventually prevent it in the next generations.  This award allows me to fund fellows from any country who are interested in diabetes research. 

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

It is a very exciting time in the field of metabolism research.  New tools and technologies are becoming available and streamlined to make major discoveries and 'translate' basic science findings to the clinic more rapidly.  Genomics, proteomics and metabolomics will all contribute importantly to finding the causes of diabetes and pointing investigators to possible new treatments.