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United States Department of Agriculture

Agricultural Research Service

Research Project: IMPACT OF EARLY DIETARY FACTORS ON CHILD DEVELOPMENT AND HEALTH

Location: Arkansas Children's Nutrition Center

Title: Insulin resistance in SD rats chronically treated with ethanol

Authors
item Badger, Thomas -
item Ferguson, Matthew -
item Ronis, Martin -

Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: December 5, 2008
Publication Date: March 1, 2009
Citation: Badger, T.M., Ferguson, M.E., Ronis, M.J. 2009. Insulin resistance in SD rats chronically treated with ethanol [abstract]. The Toxicologist. 108(1):281. Abstract No. 1362.

Interpretive Summary: Data from clinical epidemiological studies of alcohol intake and risks of type 2 diabetes/cardiovascular disease suggest that there is a u-shaped relationship, with decreased risk at low levels of intake associated with social drinking (1-2 drinks/d) compared to increased risk at intakes associated with alcoholism. This is part of the so-called French Paradox (lower mortality and heart disease in the French despite high saturated fat intake). We have previously shown that insulin resistance in the liver develops at high blood ethanol concentrations (BECs) when alcohol is infused into rats via a stomach tube (enteral feeding). However, BECs do not attain a steady state, but rather cycle with peaks of high BEC and troughs of almost no BECs despite continuous dosing. The current study was designed to determine if in addition to insulin resistance in the liver, whole body insulin resistance (mainly determined by glucose transport into skeletal muscle and fat) also changes according to BEC level during BEC cycles after chronic ethanol exposure. To measure whole body insulin resistance we conducted clamp experiments in which insulin is infused intravenously to maintain constant blood glucose levels. The rate of insulin infusion required to maintain a steady state is a measure of insulin resistance. Our preliminary data suggest that whole body insulin resistance occurs after chronic ethanol exposure at both peaks and troughs of BEC. Therefore, regulation of whole body insulin resistance and insulin resistance in the liver after alcohol treatment appears to occur via different mechanisms.

Technical Abstract: We have previously demonstrated that hepatic insulin signaling is disrupted in Sprague-Dawley (SD) rats fed EtOH-containing diets by total enteral nutrition (TEN). To determine if whole body insulin resistance could be demonstrated in the TEN model, we conducted euglycemic-hyperinsulinemic clamp studies in adult (age 90 days) rats chronically (4 weeks) fed ethanol-containing diets (10-13 g/kg/d EtOH). Rats were fed either control diets formulated to meet the National Research Council recommended daily nutrient intake for rats, or an isocaloric diet containing 10-13 g/kg/d EtOH (EtOH calories replaced a portion of the carbohydrate calories). The glucose infusion rate (GIR) of rats chronically fed >10 g/kg/d ethanol was lower (P<0.05) than control rats receiving the same isocaloric diet without ethanol. Because blood ethanol concentrations (BECs) of rats in the TEN model are pulsatile (i.e., EtOH concentrations occur as large pulses over a 6-day period), insulin clamp studies were conducted at different stages of the pulse (i.e., different BECs), and preliminary data suggest that insulin sensitivity does not vary with differences in BECs. We conclude that chronic ethanol intake causes whole body insulin resistance, and while consistent with previous data demonstrating disruption of hepatic insulin signaling, these data suggest that insulin sensitivity does not vary throughout the EtOH pulse and therefore does not drive EtOH metabolism as previously predicted.

Last Modified: 4/16/2014
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