Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Oct 12;14(10):1292.
doi: 10.3390/life14101292.

Glucagon, Metabolic Dysfunction-Associated Steatotic Liver Disease and Amino Acids in Humans and Animals without Diabetes Mellitus-An Evidence Map

Katharina Maruszczak  1   2 , Pia Koren  1 , Konrad Radzikowski  1 , Thomas Pixner  2   3 , Malte Palm Suppli  4 , Nicolai J Wewer Albrechtsen  5 , Daniel Weghuber  1   2 , Gabriel Torbahn  1   2   6
Affiliations
Review

Glucagon, Metabolic Dysfunction-Associated Steatotic Liver Disease and Amino Acids in Humans and Animals without Diabetes Mellitus-An Evidence Map

Katharina Maruszczak et al. Life (Basel). .

Abstract

Introduction: Health systems are confronted with not only the growing worldwide childhood obesity epidemic but also associated comorbidities. These subsequently cause variations in distinct metabolic pathways, leading to metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this evidence map is to systematically evaluate the evidence and to identify research gaps on glucagon-induced amino acid (AA) turnover and its metabolic interaction with MASLD.

Methodology: A systematic literature search was conducted up to April 2023 in three electronic databases. Studies were required to include at least two of the main research areas, glucagon, AA metabolism and MASLD. Two independent reviewers screened titles and abstracts according to prespecified eligibility criteria, as well as full-text articles. Results are summarized in tables stratified by human and animal studies and study population age.

Results: Thirty-four references were ultimately included. The publication years dated back to 1965 showed a great increase from 2012 to 2023. In total, there were 19 animal studies and 15 human studies. Among the human studies, except for two studies in adolescents, all the studies were conducted in adults. In human studies, the methods used to evaluate metabolic changes differed among hyperinsulinemic-euglycemic clamp and oral glucose tolerance tests. Thirteen studies focused on the metabolic effects of MASLD, while only two studies explored the interaction between MASLD, glucagon and AA metabolism in humans. The other 19 studies focused on metabolomics, beta cell function or just one topic of a research area and not on interactions between one another.

Conclusion: Research on the interaction between MASLD, glucagon and AA metabolism in humans is sparse and complete lacking in pediatrics. Furthermore, longitudinal studies with a focus on hyperglucagonemia independent of diabetes but related to MASLD present an unambiguous research gap.

Keywords: MASLD; amino acid; glucagon; liver; liver-alpha cell; pediatric.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Identification of studies via databases [21,22] and study characteristics.
Figure 2
Figure 2
Publication frequency of the liver-alpha cell axis over the past 50 years.
Figure 3
Figure 3
Venn diagram presenting the intersection of the three main search categories NAFLD, amino acids metabolism (AAM) and alpha cell function (ACF) for all ages including human and animal studies.
Figure 4
Figure 4
Limitations of human and animal studies illustrating evidence gaps.
See this image and copyright information in PMC

References

    1. Kimball C.P., Murlin J.R. Aqueous Extracts of Pancreas Iii. Some Precipitation Reactions of Insulin. J. Biol. Chem. 1923;58:337–346. doi: 10.1016/S0021-9258(18)85474-6. - DOI
    1. Rix I., Nexøe-Larsen C., Bergmann N.C., Lund A., Knop F.K. Glucagon Physiology. MDText.com, Inc.; South Dartmouth, MA, USA: 2000.
    1. Cherrington A.D., Chiasson J.L., E Liljenquist J., Jennings A.S., Keller U., Lacy W.W. The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog. J. Clin. Investig. 1976;58:1407–1418. doi: 10.1172/JCI108596. - DOI - PMC - PubMed
    1. Pedersen N., Jonsson L., Holst J.J. Necrolytic migratory erythema and glucagon cell tumour of the pancreas: The glucagonoma syndrome. Report of two cases. Acta Derm.-Venereol. 1976;56:391–395. doi: 10.2340/0001555556391395. - DOI - PubMed
    1. Norton J.A., Kahn C.R., Schiebinger R., Gorschboth C., Brennan M.F. Amino acid deficiency and the skin rash associated with glucagonoma. Ann. Intern. Med. 1979;91:213–215. doi: 10.7326/0003-4819-91-2-213. - DOI - PubMed

LinkOut - more resources