{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:36Z","timestamp":1784557056984,"version":"3.55.0"},"reference-count":47,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver\u2013\u03b1 cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver\u2013\u03b1 cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using\n                      <jats:sup>1<\/jats:sup>\n                      H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Individuals with NAFLD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952) had higher plasma glucagon concentrations than individuals without NAFLD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200958). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance\n                      <jats:italic>per se<\/jats:italic>\n                      induce these changes remains to be elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-23-0161","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T10:12:07Z","timestamp":1699611127000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":7,"title":["Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease"],"prefix":"10.1530","volume":"13","author":[{"given":"Iben","family":"Rix","sequence":"first","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"Zealand Pharma A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Herlev Hospital, University of Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asger","family":"Lund","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte P","family":"Suppli","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Chabanova","sequence":"additional","affiliation":[{"name":"Department of Radiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"van Hall","sequence":"additional","affiliation":[{"name":"Clinical Metabolomics Core Facility, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-5753","authenticated-orcid":true,"given":"Nicolai J","family":"Wewer Albrechtsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kistorp","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":true,"given":"Filip K","family":"Knop","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of Clinical Investigation","first-page":"4","article-title":"Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover","volume":"122","author":"Unger","year":"2012","unstructured":"Unger RH & Cherrington AD. 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