News & Research

    University of California, San Diego, California

ADA Mentor-based Fellowship Program

General Research Subject: Type 2 Diabetes

Focus: Genetics

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2009

Project End Date: June 30, 2013

Diabetes Type: Type 2 diabetes

Research Description

This training program encompasses a combined in vitro and in vivo approach emphasizing basic research, animal research, and classical clinical investigation.  This program will offer trainees an opportunity to conduct basic research on genetically manipulated mice and rats, as well as cellular systems in which specific gene products are overexpressed or deleted.  In addition, molecular studies in various cellular systems to elucidate  detailed signaling pathways of insulin and growth factor action are ongoing.  In the clinical research setting, functional genomic studies to understand the genetic networks contributing to insulin resistance and the therapeutic effects of insulin sensitizers are an important emphasis.  Other studies include clinical investigation of post-menopausal women with and without estrogen treatment to deduce the mechanisms whereby estrogen protects women from fat induced insulin resistance.  Taken together, this combination of basic and clinical investigation, supplemented by the ample resources and rich diabetes research environment at UCSD, provides a fertile program to allow trainees to develop their full scientific potential.

Research Profile

Mentor: Jerrold Olefsky   Postdoctoral Fellow: Andrew Johnson

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 focuses on the response of the intestine to the challenge of a high fat diet. Emerging evidence has suggested that the nature of this response is critical to the onset and development of diabetes. In particular, the intestine becomes permeable or “leaky”, allowing the bacteria which live there to spread into the rest of the body. In this way, the invading bacteria can trigger the systemic inflammation which underlies the development of diabetes. Similarly, recent evidence has shown that the “type” of bacteria which inhabit the intestine and their behavior changes during obesity and diabetes; a phenomenon referred to as “dysbiosis”. Early evidence suggests that reversing this dysbiosis can be treat some of the symptoms of diabetes. Our aim is to work out why the intestine becomes permeable to bacteria, why the type of bacteria in the intestine changes and how we can prevent these two things from occuring. Ultimately, preventing or reversing these intestinal changes would remove the driving force cusing diabetes and so offer the potential to cure or treat diabetes.

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

If we can better understand how we interact with the bacteria in our intestine we can manipulate them therapeutically to treat/prevent diabetes. This is already being attempted a crude level, replacing all the bacteria using a procedure referred to as “fecal transplant”, or getting rid of all the bacteria using antibiotics, with moderate success. However, it would obviously be preferable if we could selectively alter just the most important bacteria or get those that are already there to behave differently, for example by drinking specially designed yoghurt containing specific bacteria (probiotic) or specific dietary compounds (prebiotics). Our work will help towards that goal.

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

Needless to say, discoveries with clear therapeutic potential offer great personal satisfaction. The obesity and diabetes epidemic currently taking place across the globe is arguably the greatest health challenge of our generation. It is therefore very important for me to be part of tackling it. This award will offer finance and more importantly integrate me into a research network to enhance our collective effort.

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

It is clear that the intestinal response and the associated bacteria are key in underlying many diseases and I really believe the potential for novel therapies in this area is substantial. It is very clear however that diabetes can be caused by many factors and finding one single underlying defect in everybody with diabetes is unlikely to be realistic. Further study of how our diet can cause inflammation, how our dietary habits develop and how they can be changed (e.g. by altering appetite) will be critical avenues of future research.