Rahmouni, Kamal , Ph.D.
Mechanisms Mediating the Metabolic Effects of Amylin Action in the Brain
General Research Subject: Obesity
Focus: Integrated Physiology\GLP-1, GIP, and Other Gut Hormones, Obesity\Animal Models
Type of Grant: Basic Science
Project Start Date: January 1, 2011
Project End Date: December 31, 2013
The increasing prevalence of obesity is a serious health hazard and represents a growing public health concern. This is particularly true for the United States where the steady rise in overweight and obesity is expected to reduce longevity and become the leading cause of death. Obese individuals are at increased risk for diabetes, cardiovascular diseases and certain forms of cancer. It has become evident over the past decades that the obesity epidemic cannot only explained by genetic predisposition. Other causes related to lifestyle, nutrition and changes in physical activity or environmental factors seem involved. Numerous peripheral signals contribute to the regulation of food intake and energy homeostasis by altering the activity of the fuel sensing neurons in the brain. The focus of this project is to understand the brain effects of amylin, a hormone released from the pancreas, on metabolism and energy expenditure. Broad array of techniques will be employed to define the molecular and neural mechanisms mediating the regulation of peripheral metabolism by amylin action in the brain. The more we know about the mechanisms mediating the metabolic effects of amylin, the more likely it is that we can understand the mechanisms of energy imbalance and metabolic disorders associated with obesity and type 2 diabetes which will ultimately improve treatments.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Amylin is a hormone produced and secreted by the same pancreatic cells that make insulin. Amylin participates in the regulation of glucose homeostasis by complementing the actions of insulin. We also know that amylin act in the brain to control food intake and body weight. However, we know very little about the pathways and mechanisms used by amylin to regulate glucose metabolism, food intake and body weight. To fill this gap, we designed this research project to understand how amylin action in the brain controls peripheral metabolism and energy expenditure. The availability to us of unique tools and broad array of techniques provide us with a novel opportunity to investigate the importance of amylin action in the brain and define the molecular and neural pathways mediating the regulation of peripheral metabolism by amylin. Deciphering the neural and molecular pathways that underlie the control of metabolism by amylin will help manage obesity-associated diabetes and other disorders. Expanding our fundamental knowledge of the physiological and pathological effects of amylin could also pave the way for clinical use of amylin in metabolic disorders.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
To understand the etiology of obesity, and to discover new therapies for energy imbalance, we must first understand the components and mechanisms regulating metabolism. The more we know how hormones such as amylin regulate glucose metabolism, food intake and energy expenditure, the more likely it is that we can understand why diabetes and metabolic disorder are commonly associated with obesity. Such information will help manage patients with obesity and diabetes and ultimately improve treatments. A better understanding the pathways used by amylin to control energy homeostasis and glucose metabolism will offer the possibility to selectively interfere with those pathways to enhance the beneficial effects.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My research has been focused on understanding the links between obesity, high blood pressure and cardiovascular diseases. Building upon our success in depicting the alterations that increases the cardiovascular risk and subsequent target-organ damage in obesity, the current Award will provide me with a unique opportunity to expand my research to diabetes and related disorders. We will develop and use state-of-the-art concepts, methods, and strategies developed by us and others to identify the key factors and pathways involved in glucose metabolism and insulin sensitivity which holds great promise for increasing our understanding of the etiology of diabetes and obesity. This research could point to novel interventions to be used for the prevention or treatment of metabolic abnormalities and related disorders. Working in health care environment, I often hear the frustration of the physicians who are dealing with patients suffering from metabolic-related illnesses about the lack of appropriate approaches and strategies to deal with those diseases. This represents an important factor in defining the direction of my research and the problems to tackle.
In what direction do you see the future of diabetes research going?
The increasing prevalence of obesity is a serious health hazard and represents a growing public health concern. Fortunately, the knowledge about the network and biological mechanisms that regulate metabolic processes is expanding at a remarkable pace. This combined with the tremendous progress in translational research provide reasons to hope that effective pharmacological approaches to manage obesity will soon emerge. Designing novel therapeutic strategies to treat obesity without causing undesirable cardiovascular and metabolic side effects will be challenging, but necessary. Some of the most effective anti-obesity drugs are no longer licensed for use in humans due to undesirable cardiac and metabolic complications. My work regarding the possibility to dissociate the pathways that control metabolism versus those are relevant for cardiovascular regulation is an indication that this is feasible.
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