Mercury as an Insulin Mimic: Mechanism of Action and Potential Physiological Consequences

EPA Grant Number: R825218
Title: Mercury as an Insulin Mimic: Mechanism of Action and Potential Physiological Consequences
Investigators: Barnes, David M.
Institution: University of Arkansas - Fayetteville
EPA Project Officer: Hahn, Intaek
Project Period: November 15, 1996 through November 14, 2001
Project Amount: $481,991
RFA: Exploratory Research - Early Career Awards (1996) RFA Text |  Recipients Lists
Research Category: Early Career Awards

Description:

Polypeptide hormones are important in the regulation of many metabolic processes; however, little is known regarding the ability of environmental pollutants to disrupt polypeptide hormone action. Although information regarding the hormone-like effects of heavy metals is limited, preliminary data reveal that mercury induces hexose transport and increases protein synthesis with patterns, magnitudes, and kinetics identical to those of insulin. Mercury's insulin-like effects and extended half-life in the body may lead to a chronic stimulation of the insulin signal transduction pathway which either may initiate or prevent the normal feedback mechanisms that regulate insulin responses. Alterations of these normal feedback mechanisms could result in a long-term modulation of insulin responsiveness. This project hypothesizes that mercury acts as an insulin-mimic which initiates insulin-like effects by specifically activating insulin-responsive signal transduction pathways, thus, providing an environmental component which leads to the downregulation of insulin-mediated effects. This hypothesis will be addressed with the following objectives: 1) to compare the effects of mercury and insulin on hexose transport and protein synthesis in hepatocyte, adipocyte, and skeletal muscle cell lines, representing the tissues involved in glucose homeostasis; 2) to determine the signal transduction pathway(s) targeted by mercury to induce its insulin-like effects; and 3) to determine if prolonged exposure to mercury induces cells to become nonresponsive to subsequent stimulation with insulin. These objectives will be addressed by following the uptake and the incorporation of radiolabelled tracers and by analyzing the biochemical effects of mercury on insulin-stimulated signal transduction enzymes. This study will further our understanding of the insulin-like effects of mercury its potential to disrupt insulin regulated metabolism. Moreover, these results will contribute to a better understanding of the ability of xenobiotics to function as hormone-mimics and may contribute to an understanding of the role of environmental factors in the induction of diseases or dysfunctions associated with insulin nonresponsiveness.

Supplemental Keywords:

heavy metals, biochemical pathway, aquatic frog., RFA, Scientific Discipline, Health, Water, Environmental Chemistry, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Biochemistry, Children's Health, Endocrine Disruptors - Human Health, Mercury, aquatic, hexose transport, metabloic processes, signal transduction pathways, endocrine disrupting chemicals, insulin mimic, protein synthesis, human exposure, Physicochemical aspects, polypeptide hormones, biochemical pathway, transduction enzymes

Progress and Final Reports:

  • 1997
  • 1998
  • 1999
  • 2000
  • Final