Li, Ji , Ph.D., FAHA
Aging-associated alterations in ischemic glucose transport by the MIF-AMPK pathway
General Research Subject: Type 2 Diabetes
Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Integrated Physiology\Muscle, Integrated Physiology\Regulation of Glucose Kinetics
Type of Grant: Basic Science
Project Start Date: January 1, 2011
Project End Date: December 31, 2013
Diabetes Type: Type 2 diabetes
Why is there a high incidence for both diabetes and cardiovascular disease in aging populations? In this proposal the investigators have shown that AMP-activated protein kinase (AMPK) signaling plays an important role not only in regulating muscle glucose transport but also ameliorating cardiac dysfunction induced by ischemic stress. This group has also revealed an important role of macrophage migration inhibitory factor (MIF), shown to cooperate with AMPK signaling in restraining myocardial damage and dysfunction following ischemic stress. Moreover, an aging-associated reduction in AMPK activity has been speculated to contribute to reduced mitochondrial function, thereby dysregulating energy metabolism.
It has been further hypothesized that aging is associated with a decline in the ability of cardiac cells to activate the host defense response to acute ischemic injury, via the MIF-AMPK cascade, resulting in a reduced tolerance to such stress on the heart. Their proposed research project will address whether defective AMPK activation with aging leads to impaired glucose metabolism in the heart and whether or not this increases the susceptibility of the myocardium to injury. These studies will elucidate the potential role of glucose metabolism in cardiovascular disease in the elderly. Therefore, by investigating the physiological role of impaired activation of cardiac AMPK and glucose metabolism during ischemia/reperfusion with aging, they hope to enhance our understanding of the relationship between aging, diabetes, and cardiovascular disease in order to develop new therapeutic strategies.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project covers the cardiovascular complications of diabetes with aging. These studies will specifically elucidate the role of glucose metabolism in cardiovascular disease in the elderly. Therefore, by investigating the physiological role of impaired activation of energetic signaling and glucose metabolism in the heart during ischemia/reperfusion with aging, we hope to enhance our understanding of the relationship between aging, diabetes, and cardiovascular disease in order to develop new therapeutic strategies for aging-related diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
We are trying to address why there is a high incidence for both diabetes and cardiovascular disease in aging populations. This project may uncover compounds that augment macrophage migration inhibitory factor (MIF) dependent AMP-activated protein kinase (AMPK) activation offering protection against diabetes and diabetes-associated cardiovascular diseases by modulating the MIF-AMPK signaling pathway.
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 really enjoying the ongoing cardiovascular research in my lab. One of the major reasons leading to cardiovascular complications is diabetes, therefore, we really want to know how this metabolic disorder occurs and how it affects the cardiovascular diseases such as ischemic heart disease.
This award will definitely provide an opportunity to reach one goal of our aging cardiovascular research program, i.e. to enhance the understanding of the relationship among diabetes, aging, and ischemic heart disease; therefore keeping aged individuals with ischemic heart disease living longer.
In what direction do you see the future of diabetes research going?
Insulin has been around since 1921, and we need alternative products to replace insulin.
Importantly, we should first find out the signaling mechanisms of regulating glucose uptake, to provide ideal targets for developing insulin mimic drugs for treatment of diabetes.
All investigators need to work together in order to set up strong research programs aimed at benefiting people with all stages of diabetes. We especially need to put efforts on addressing the molecular mechanisms of age-related diabetes and cardiovascular disease so that we can deliver and offer both short-term and long-term treatments, cures, and solutions. The ultimate goal of us as scientists is to cure, treat, and prevent diabetes.
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