News & Research

    The University of Texas Medical Branch, Galveston, Texas

Role of hydrogen sulfide in diabetic vascular complications

General Research Subject: Type 2 Diabetes

Focus: Complications, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes, Complications\Nephropathy, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Cytokines and Apoptosis

Type of Grant: Basic Science

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Hydrogen sulfide (H2S), an eggy-smelling toxic gas, is the byproduct of swamps, volcanic emissions and industrial processes. However, recently, various roles of H2S are emerging in the regulation of key functions of the human body. H2S is produced by cells of animals and humans, and plays important protective roles in the control of our blood circulation. In both Type 1 and Type 2 diabetes, there are various disturbances in the circulatory system, and much of this is due to the fact that the blood vessels are exposed to unusually high levels of circulating sugar for prolonged periods. This damages the blood vessels, especially in the inner layer (endothelial cells). When endothelial cells are damaged, the circulatory system suffers various injuries, and the endothelial injury leads to problems with the heart, kidneys, eyes, and impairs the circulation to the legs.

We have discovered that endothelial cells placed in high sugar develop a problem in their ability to maintain protective levels of H2S, and this results in cell damage. Based on new preliminary data, we propose that therapy with H2S in diabetes can be beneficial. In the current proposal, we propose two areas of investigation, which will be conducted in parallel. First, we propose to find out how H2S improves endothelial function on the molecular level. Second, we propose to test if treatment of diabetic animals with H2S protects their blood vessels, kidneys and hearts. Our project is highly relevant diabetic patients, it can open a novel therapeutic approach for diabetic complications.

Research Profile

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

Hydrogen sulfide (H2S), an eggy-smelling toxic gas, is the byproduct of swamps, volcanic emissions and industrial processes. However, recently, various roles of H2S are emerging in the regulation of key functions of the human body. H2S is produced by cells of animals and humans, and plays important protective roles in the control of our blood circulation. In both Type 1 and Type 2 diabetes, there are various disturbances in the circulatory system, and much of this is due to the fact that the blood vessels are exposed to unusually high levels of circulating sugar for prolonged periods. This damages the blood vessels, especially in the inner layer (endothelial cells). When endothelial cells are damaged, the circulatory system suffers various injuries, and the endothelial injury leads to problems with the heart, kidneys, eyes, and impairs the circulation to the legs. We have discovered that endothelial cells placed in high sugar develop a problem in their ability to maintain protective levels of H2S, and this results in cell damage.

Based on new preliminary data, we propose that therapy with H2S in diabetes can be beneficial. In the current proposal, we propose two areas of investigation, which will be conducted in parallel. First, we propose to find out how H2S improves endothelial function on the molecular level. Second, we propose to test if treatment of diabetic animals with H2S protects their blood vessels, kidneys and hearts. Our project is highly relevant diabetic patients, it can open a novel therapeutic approach for diabetic complications.

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

Recent research shows that hydrogen sulfide (H2S), an eggy-smelling gas, is produced by the body and is important in maintaining the function of blood vessels. We have discovered that the body's H2S level is diminished in cell and animal models of diabetes, and we have data that suggest that replacement of H2S may be a possible future therapy to prevent or to attenuate diabetic complications of blood vessels. The current research seeks to address this fundamental novel concept. First, we will find out how H2S improves endothelial function (this is the most important part of blood vessels, and one that gets damaged during diabetes) on the molecular level. Second, we will test if treatment of diabetic animals with H2S protects their blood vessels, kidneys and hearts. Our project is highly relevant diabetic patients, as it can open a novel therapeutic approach for diabetic complications. There are already many experimental compounds and natural extracts that contain H2S, or molecules that release H2S. Once we have established this new concept, these molecules will allow a relatively fast translation of the work to the bedside.

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

I have started working on diabetes in 2000, shortly after my father was diagnosed with Type II diabetes. Before that, I studied the function of blood vessels, and I was involved in studies of free radicals and inflammatory processes, but have not worked in the area of diabetes. I started collaborating with experts in the field of diabetic complications and have learned as much as possible from them, as well as from the literature, and have started doing my own experiments in this area. I believe that I have made significant progress in this field, and discovered several pathways (PARP, peroxynitrite, and, most recently, H2S) and published many papers that are now often cited in the literature.

The current grant award will be the first one to support my work on the role of H2S in diabetic complications. H2S is a rapidly emerging field of biology; I have substantial expertise in the biology of H2S and the current award will help my group study and establish a novel therapeutic concept in this area. We have managed to collect significant preliminary data in this area, and in late 2011 we have published a paper in a premier journal (PNAS), but without grant support, we could have not continued this line of research. I am extremely glad and grateful for the ADA's decision to realize the scientific and potential future therapeutic importance of this area.

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

I cannot comment on all aspects of diabetes research, so I would like to focus on my own area, which is diabetic cardiovascular complications. I believe that the endothelial cell, as the 'maestro' of blood vessels and blood circulation, and as a primary 'victim' of diabetic injury, will remain a central area of investigation. I believe that much of the future's work will focus on diabetic metabolic memory (the process whereby diabetic complications, once they begin, continue and are very hard to stop). I also believe that significant future work will focus on glycemic variability (the mechanism on how sudden and repeated changes in blood sugar levels cause damage to the blood vessels). As far as mechanisms and pathways, I believe much of the future of diabetes research will, once again, focus on endogenous regulatory factors and local hormones, and will try to apply this knowledge to developing future therapeutic approaches.