All ETDs from UAB

Advisory Committee Chair

Joseph L Messina

Advisory Committee Members

Jeffrey A Engler

Robert W Hardy

Thomas M Ryan

Philip A Wood

Document Type

Dissertation

Date of Award

2009

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; 2) characterize the expression of adipose-derived cytokines and adipokines following trauma and hemorrhage; and 3) determine whether there were long-term effects on insulin signaling and the expression of adipose-derived cytokines and adipokines after resuscitation and recovery. A rat model of surgical trauma and hemorrhage was used to achieve these goals. Insulin signaling via the insulin receptor/insulin receptor substrate-1/Akt pathway was examined. There was an acute onset of insulin signaling defects in adipose tissue as early as 15 min following hemorrhage which persisted for at least 90 min. During the hemorrhage period, there were no consistent and persistent alterations in the adipose-derived cytokines and adipokines that were examined. At the end of the 24 h recovery period, adiponectin mRNA was notably decreased and IL-1β mRNA was increased. The studies in this dissertation provide evidence for the acute onset of adipose tissue insulin resistance following trauma and hemorrhage. Additional evidence is provided that adipose tissue-derived cytokines and adipokines do not play key roles in the development of insulin resistance, but may in fact play important roles in maintaining insulin resistant states. Hyperglycemia in critically ill patients is associated with a poor outcome. Controlling hyperglycemia has been demonstrated to reduce morbidity and mortality. Thus, understanding the role of adipose tissue in insulin resistance may assist in the development of therapeutic interventions to manage insulin resistance following acute injury.

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