News & Research

    University of Southern California, Los Angeles, California

Regulation of hypothalamic-pituitary-adrenal axis by free fatty acids and insulin

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Insulin Action, Insulin Action\Insulin Resistance, Integrated Physiology, Integrated Physiology\Insulin Resistance, Obesity, Obesity\Pathogenesis

Type of Grant: Basic Science

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Cortisol, also known as the "stress hormone," is an essential hormone for the maintenance of internal stability of our bodies under stressful conditions.  Cortisol is synthesized and secreted by the adrenal gland, but these processes are under the control of the brain through interactions involving the hypothalamus, pituitary, and adrenal glands, known as the hypothalamic-pituitary-adrenal (HPA) axis.  The HPA axis is activated by many different types of stress.  Excessive activation of the HPA axis can have detrimental effects.  In addition, increased HPA-axis activity is implicated in obesity and type 2 diabetes. 

Identification of unexplored mechanisms for HPA-axis activation would increase our understanding of how the HPA axis is activated in disease-promoting states and/or provide new targets for pharmaceutical interventions.  Our preliminary studies suggested that the HPA axis is regulated by plasma free fatty acid (FFA) and insulin levels. The objective of this proposal is to explore these novel effects of plasma FFA and insulin on the HPA axis and evaluate their physiological significance.  The results of this project could potentially identify mechanisms (i.e., impaired brain sensing of plasma FFA or insulin) for increased HPA-axis activity and/or elevated circulating FFA levels in obesity and type 2 diabetes.

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?

This project covers the area of metabolic and hormonal changes associated with type 2 diabetes.  Specifically, we will investigate the mechanisms by which cortisol secretion is regulated by plasma free fatty acid (FFA) or insulin levels.  Cortisol, also known as the "stress hormone," is an essential hormone for the maintenance of internal stability of our bodies under stressful conditions.  Cortisol is synthesized and secreted by the adrenal gland, but these processes are under the control of the brain through interactions involving the hypothalamus, pituitary, and adrenal glands, known as the hypothalamic-pituitary-adrenal (HPA) axis.  Excessive activation of the HPA axis can have detrimental effects. 

In addition, increased HPA-axis activity is implicated in obesity and type 2 diabetes.   Our preliminary studies suggested that the HPA axis is regulated by plasma FFA and insulin levels. The objective of this proposal is to explore these novel effects and evaluate their physiological significance.  Identification of unexplored mechanisms for HPA-axis activation would increase our understanding of how the HPA axis is activated in disease-promoting states and/or provide new targets for pharmaceutical interventions.

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

Cortisol, also known as the "stress hormone," is an essential hormone for the maintenance of internal stability of our bodies under stressful conditions.  However, excessive cortisol has detrimental effects.  Plasma cortisol levels are elevated in patients with type 2 diabetes, contributing to metabolic derangements, but the underlying mechanisms are unclear.  This project will explore previously unknown effects of plasma free fatty acid (FFA) and insulin levels on cortisol secretion.  The results of this project could potentially identify mechanisms for increased cortisol secretion in type 2 diabetes and provide new targets for pharmaceutical interventions. 

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

It is important for me, personally, to become involved in diabetes research because I have a family history of diabetes. 

The proposed studies represent a new research direction for me.  This award will provide a crucial support for this new direction exploring novel mechanisms for regulation of cortisol secretion, which could be further developed into a solid diabetes research program supported by NIH. 

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