Estimating glucose requirements of an activated immune system in growing pigs

摘要

Activated immune cells become obligate glucose utilizers, and a large i.v. lipopolysaccharide (LPS) dose causes insulin resistance and severe hypoglycemia. Therefore, study objectives were to quantify the amount of glucose needed to maintain euglycemia following an endotoxin challenge as a proxy of leukocyte glucose requirements. Fifteen fasted crossbred gilts (30.3 ± 1.7 kg) were bilaterally jugular catheterized and assigned 1 of 2 i.v. bolus treatments: control (CON; 10 mL sterile saline; n = 7) or LPS challenge + euglycemic clamp (LPS-Eu; Escherichia coli 055:B5; 5 μg/kg BW; 50% dextrose infusion to maintain euglycemia; n = 8). Following administration, blood glucose was determined every 10 min and dextrose infusion rates were adjusted in LPS-Eu pigs to maintain euglycemia for 8 h. Pigs were fasted for 8 h prior to the bolus and remained fasted throughout the challenge. Rectal temperature was increased in LPS-Eu pigs relative to CON pigs (39.8 vs. 38.8°C; P < 0.01). Relative to the baseline, CON pigs had 20% decreased blood glucose from 300 to 480 min postbolus (P = 0.01) whereas circulating glucose content in LPS-Eu pigs did not differ (P = 0.96) from prebolus levels. A total of 116 ± 8 g of infused glucose was required to maintain euglycemia in LPS-Eu pigs. Relative to CON pigs, overall plasma insulin, blood urea nitrogen, β-hydroxybutrate, L-lactate, and LPS-binding protein were increased in LPS-Eu pigs (295, 108, 29, 133, and 13%, respectively; P ≤ 0.04) whereas NEFA was decreased (66%; P < 0.01). Neutrophils in LPS-Eu pigs were decreased 84% at 120 min postbolus and returned to CON levels by 480 min (P < 0.01). Overall, lymphocytes, monocytes, eosinophils, and basophils were decreased in LPS-Eu pigs relative to CON pigs (75, 87, 70, and 50%, respectively; P ≤ 0.05). These alterations in metabolism and the large amount of glucose needed to maintain euglycemia indicate nutrient repartitioning away from growth toward the immune system. Glucose is an important fuel for the immune system, and data from this study established that the glucose requirements of an intensely and acutely activated immune system in growing pigs are approximately 1.1 g/kg BW^0.75/h.