The relationship between glucose and the liver-alpha cell axis - A systematic review.

Dieter Furthner, Andreas Lukas, Harald Mangge, Thomas Pixner, Nathalie Stummer, Anna Maria Schneider, Karin Gramlinger, Valérie Julian, David Thivel, Katharina Mörwald, Christopher Dalus, Elmar Aigner, Daniel Weghuber, Katharina Maruszczak

Journal: Frontiers in endocrinology 2023;13():1061682

PMID: 36686477

Abstract

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.

Copyright © 2023 Pixner, Stummer, Schneider, Lukas, Gramlinger, Julian, Thivel, Mörwald, Mangge, Dalus, Aigner, Furthner, Weghuber and Maruszczak.

Address: Department of Pediatric and Adolescent Medicine, Salzkammergutklinikum Voecklabruck, Voecklabruck, Austria.; Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.; Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.; Department of Sport Medicine and Functional Explorations, Diet and Musculoskeletal Health Team, Human Nutrition Research Center (CRNH), INRA, University Hospital of Clermont-Ferrand, University of Clermont Auvergne, Clermont-Ferrand, France.; Laboratory of Metabolic Adaptations to Exercise under Physiological and Pathological Conditions (AME2P), University of Clermont Auvergne, Clermont-Ferrand, France.; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.; First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.
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