RUI: Glucose Production and Disposal During Long Term Fasting Northern Elephant Seals.

Sonoma State University, Rohnert Park CA

Investigators

Abstract

A major challenge of long-term fasting is the provision of glucose for glucose-dependent tissues (e.g. central nervous system) while sparing protein in vital body organs. Seals provide an excellent system to investigate metabolic strategies during fasting because they undertake natural fasts during periods that elevate nutrient demands. Weaned northern elephant seals fast for 2-3 months, during which time physiological development supporting their diving ability occurs. Previous investigations in this system revealed a number of unique features of metabolism that differ from the traditional view of fasting adaptation. Despite efficient protein sparing, plasma glucose levels in elephant seals are high throughout the fast. Levels of glucose production fail to exhibit the suppression with fasting that is seen in other species. Breakdown of protein and fats provides only a small portion of this glucose production and, therefore, the source of this endogenous glucose production has not been identified. This research project will investigate glucose production and disposal during long-term natural fasts in northern elephant seals. Isotopic tracer techniques and respirometry will be combined to 1) examine the contribution of various substrates to glucose production 2) examine the metabolic strategies for glucose clearance 3) examine variation in fuel use over fasting period and 4) examine the activity of several key metabolic cycles that may regulate glucose production. This study will provide important information about the metabolic strategies that enable long-term fasting during development. Increased understanding of the novel features of carbohydrate regulation in fasting-adapted animals, including maintenance of high blood glucose while fasting, avoidance of ketoacidosis, protein sparing despite high rates of glucose production, and high rates of glucose disposal despite low insulin levels and insulin resistance can potentially inform our understanding of human pathologies of carbohydrate metabolism. This research will also promote research training and education to undergraduate and graduate students, especially underrepresented minority students, through participation in exciting research on a unique wildlife system.