DRWF Research in focus: Regulating food and energy metabolism in diabetes
Dr Kang’s research focuses on studying the regulation of food and energy metabolism in health conditions, including obesity, diabetes and heart problems.
The role of adipose tissue ECM-integrin signalling (extracellular matrix) in inflammation and insulin resistance.
Tell us about your research since the Pump Priming award.
“Pump priming refers to investment of a relatively small amount of funding to generate preliminary data and ideas to secure more funding in the future. It is a proof-of-concept award.
“My research investigates the role of adipose tissue ECM-integrin signalling (extracellular matrix) in inflammation and insulin resistance.
“Most of the cells in our body use glucose for energy along with fat and amino acids, which are the building blocks of protein. Cells can convert glucose to energy molecules, for example ATP (adenosine triphosphate), through a process called cellular respiration. ATP is the usable form of energy for our cells.
“Insulin is a hormone coming from the pancreas, which helps glucose to be delivered and taken up by cells in our tissues, for example cells in muscle and fat tissues. Insulin can also control how much glucose is produced from our liver cells, and therefore it is an important hormone controlling glucose balance in our body.
“In people with type 2 diabetes, their cells do not respond normally to insulin, and the reason behind this is still not fully understood. That is also what my research is trying to tackle. So, when cells do not respond normally to insulin, glucose cannot be sufficiently removed from the blood. For example, insulin cannot stimulate glucose to be taken up by our muscle cells where glucose is most needed for energy or taken up by the fat cells, where glucose can be stored as energy in the form of fat.
“In addition, insulin cannot efficiently communicate with the liver to shut down systems that produce glucose that will normally only occur during starvation, for example. All these problems add up and lead to an increase in blood glucose levels in people with type 2 diabetes.”
Improving cell response to insulin
“We are aiming to develop a completely new way of improving cell response to insulin in people with diabetes by studying molecules outside cells, the levels of which are increased when cells stop responding properly to insulin.
“Our cells are embedded in a network of structural proteins and molecules, and these molecules play a really important role in terms of controlling how cells move, communicate with each other and behave for normal function.
“In people with obesity and type 2 diabetes, it has been found that these structural molecules are increased, so they form an extra barrier for cells to exert normal function. For example, for insulin to be able to work, insulin needs to pass these barriers to reach cells, so this can potentially affect how the hormone insulin works.
“These increased outside structural molecules can also bind to their partner proteins on the surface of cells, which can further induce signalling changes inside the cells, which again can interfere with how insulin works once insulin gets inside the cells.
“We have studied a pathway that involves structural proteins called collagens and their cell surface binding partners called integrin and the downstream signalling molecules which are inside the cells called integrin linked kinase. We discovered that when we removed either one of the three parts in this pathway, we were able to restore insulin’s ability to remove glucose from the bloodstream and therefore lower blood glucose levels.”
How might your research findings benefit people with diabetes?
“Our research results have led us to believe that we can target these structural proteins outside the cells to develop novel treatments for obesity, diabetes and heart problems. This is because insulin resistance, the condition when insulin does not work, is a common underlying factor for all of these conditions.
“We have tried to use interventions to remove components of the structural network outside the cells and then examine how they affect insulin action and tissue function and complications of the condition, for example obesity-related conditions. So far, we have seen promising results with some of these interventions. However, these are still under the preclinical tests, and we will need further evidence before moving to clinical trials.”
How important are the DRWF Pump Priming awards?
“I started my independent research career in 2014 and had lots of grant rejections due to lack of preliminary data. I realised that I would need to apply for smaller grants to help with developing research ideas and gathering preliminary data. The DRWF Pump Priming programme caught my interest, so I applied and was subsequently successful in securing a one-year award.
“Since 2017, I have successfully secured three major project grants with two as principal investigator and one as a co-investigator. The initial DRWF award has really helped me to build the foundation of my research programme, accelerating and leveraging additional financial support to take our work to the next stage. I’m extremely grateful for the springboard that DRWF has given me.”
This article was originally published in the October 2022 edition of Diabetes Wellness News. For more information and to subscribe to the DRWF quarterly newsletter visit here
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