The Effect of Glucagon on Protein Catabolism During Insulin Deficiency: Exchange of Amino Acids Across Skeletal Muscle and the Splanchnic Bed

Haleigh James, Wilson I. Gonsalves, Shankarappa Manjunatha, Surendra Dasari, Ian R. Lanza, Katherine A. Klaus, Adrian Vella, James C. Andrews, K. Sreekumaran Nair

Research output: Contribution to journalArticlepeer-review

Abstract

Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon's catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino acid metabolites (amino-metabolites) across muscle and splanchnic beds in 16 healthy humans during either somatostatin followed by glucagon or saline infusion alone. Despite a twofold or greater increase in the regional exchange of amino-metabolites by glucagon, whole-body kinetics and concentrations of amino acids (AA) remained stable. Glucagon increased the splanchnic uptake of not only gluconeogenic but also essential (EAA) AA while increasing their release from the muscle bed. Regional tracer-based kinetics and 3-methylhistidine release indicate that EAA release from muscle is likely caused by reduced protein synthesis rather than increased protein degradation. Furthermore, many metabolites known to affect insulin action and metabolism were altered by hyperglucagonemia including increase in branched-chain AA and keto acids of leucine and isoleucine in arterial plasma. Further, an increase in arterial concentrations of α-aminoadipic acid arising from increased conversion from lysine in the splanchnic bed was noted. These results demonstrate that hyperglucagonemia during hypoinsulinemia increases net muscle protein catabolism and substantially increases the exchange of amino metabolites across splanchnic and muscle beds.

Original languageEnglish (US)
Pages (from-to)1636-1648
Number of pages13
JournalDiabetes
Volume71
Issue number8
DOIs
StatePublished - Aug 1 2022

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'The Effect of Glucagon on Protein Catabolism During Insulin Deficiency: Exchange of Amino Acids Across Skeletal Muscle and the Splanchnic Bed'. Together they form a unique fingerprint.

Cite this