Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition

Research output: Contribution to journalJournal articleResearchpeer-review

Steven E Thiessen, Sarah Derde, Inge Derese, Thomas Dufour, Chloé Albert Vega, Lies Langouche, Chloë Goossens, Nele Peersman, Pieter Vermeersch, Sarah Vander Perre, Jens J Holst, Pieter J Wouters, Ilse Vanhorebeek, Greet Van den Berghe

RATIONALE: Critical 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.

OBJECTIVES: To 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.

METHODS: In 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 RESULTS: In 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.

CONCLUSIONS: These 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).

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume196
Issue number9
Pages (from-to)1131-1143
Number of pages13
ISSN1073-449X
DOIs
Publication statusPublished - 1 Nov 2017

    Research areas

  • Aged, Amino Acids/blood, Animals, Blood Glucose, Critical Illness, Disease Models, Animal, Female, Glucagon/blood, Glucose/administration & dosage, Humans, Insulin/administration & dosage, Male, Mice, Middle Aged, Muscular Atrophy/blood, Parenteral Nutrition/methods, Treatment Outcome

ID: 190858674