• Steven E Thiessen, Sarah Derde, Inge Derese, Thomas Dufour, Vega Chloé Albert CA 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, and., Lies Langouche, Chloë Goossens, Nele Peersman, Pieter Vermeersch, Sarah Vander Perre, Jens J Holst, Pieter J Wouters, Ilse Vanhorebeek, and Greet Van den Berghe.
• 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, and.
• Am. J. Respir. Crit. Care Med. 2017 Nov 1; 196 (9): 1131-1143.

RationaleCritical illness is hallmarked by muscle wasting and disturbances in glucose, lipid, and amino acid homeostasis. Circulating concentrations of glucagon, a catabolic hormone that affects these metabolic pathways, are elevated during critical illness. Insight in the nutritional regulation of glucagon and its metabolic role during critical illness is lacking.ObjectivesTo evaluate whether macronutrient infusion can suppress plasma glucagon during critical illness and study the role of illness-induced glucagon abundance in the disturbed glucose, lipid, and amino acid homeostasis and in muscle wasting during critical illness.MethodsIn human and mouse studies, we infused macronutrients and manipulated glucagon availability up and down to investigate its acute and chronic metabolic role during critical illness.Measurements And Main ResultsIn critically ill patients, infusing glucose with insulin did not lower glucagon, whereas parenteral nutrition containing amino acids increased glucagon. In critically ill mice, infusion of amino acids increased glucagon and up-regulated markers of hepatic amino acid catabolism without affecting muscle wasting. Immunoneutralizing glucagon in critically ill mice only transiently affected glucose and lipid metabolism, did not affect muscle wasting, but drastically suppressed markers of hepatic amino acid catabolism and reversed the illness-induced hypoaminoacidemia.ConclusionsThese data suggest that elevated glucagon availability during critical illness increases hepatic amino acid catabolism, explaining the illness-induced hypoaminoacidemia, without affecting muscle wasting and without a sustained impact on blood glucose. Furthermore, amino acid infusion likely results in a further breakdown of amino acids in the liver, mediated by increased glucagon, without preventing muscle wasting. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).

33 keywords...

hide…