Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease

Research output: Contribution to journalJournal articleResearchpeer-review

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Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease. / Rix, Iben; Johansen, Marie L.; Lund, Asger; Suppli, Malte P.; Chabanova, Elizaveta; van Hall, Gerrit; Holst, Jens J.; Wewer Albrechtsen, Nicolai J.; Kistorp, Caroline; Knop, Filip K.

In: Endocrine Connections, Vol. 13, No. 1, e230161, 2023.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rix, I, Johansen, ML, Lund, A, Suppli, MP, Chabanova, E, van Hall, G, Holst, JJ, Wewer Albrechtsen, NJ, Kistorp, C & Knop, FK 2023, 'Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease', Endocrine Connections, vol. 13, no. 1, e230161. https://doi.org/10.1530/EC-23-0161

APA

Rix, I., Johansen, M. L., Lund, A., Suppli, M. P., Chabanova, E., van Hall, G., Holst, J. J., Wewer Albrechtsen, N. J., Kistorp, C., & Knop, F. K. (2023). Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease. Endocrine Connections, 13(1), [e230161]. https://doi.org/10.1530/EC-23-0161

Vancouver

Rix I, Johansen ML, Lund A, Suppli MP, Chabanova E, van Hall G et al. Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease. Endocrine Connections. 2023;13(1). e230161. https://doi.org/10.1530/EC-23-0161

Author

Rix, Iben ; Johansen, Marie L. ; Lund, Asger ; Suppli, Malte P. ; Chabanova, Elizaveta ; van Hall, Gerrit ; Holst, Jens J. ; Wewer Albrechtsen, Nicolai J. ; Kistorp, Caroline ; Knop, Filip K. / Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease. In: Endocrine Connections. 2023 ; Vol. 13, No. 1.

Bibtex

@article{39270f581d144184b5da8e444b760c4f,
title = "Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease",
abstract = "Aims: 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–α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver–α 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.Methods: We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.Results: Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). 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.Conclusion: 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 per se induce these changes remains to be elucidated.",
keywords = "amino acids, glucagon, humans, non-alcoholic fatty liver disease, type 2 diabetes mellitus",
author = "Iben Rix and Johansen, {Marie L.} and Asger Lund and Suppli, {Malte P.} and Elizaveta Chabanova and {van Hall}, Gerrit and Holst, {Jens J.} and {Wewer Albrechtsen}, {Nicolai J.} and Caroline Kistorp and Knop, {Filip K.}",
note = "Publisher Copyright: {\textcopyright} 2023 the author(s).",
year = "2023",
doi = "10.1530/EC-23-0161",
language = "English",
volume = "13",
journal = "Endocrine Connections",
issn = "2049-3614",
publisher = "BioScientifica Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease

AU - Rix, Iben

AU - Johansen, Marie L.

AU - Lund, Asger

AU - Suppli, Malte P.

AU - Chabanova, Elizaveta

AU - van Hall, Gerrit

AU - Holst, Jens J.

AU - Wewer Albrechtsen, Nicolai J.

AU - Kistorp, Caroline

AU - Knop, Filip K.

N1 - Publisher Copyright: © 2023 the author(s).

PY - 2023

Y1 - 2023

N2 - Aims: 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–α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver–α 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.Methods: We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.Results: Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). 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.Conclusion: 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 per se induce these changes remains to be elucidated.

AB - Aims: 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–α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver–α 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.Methods: We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.Results: Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). 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.Conclusion: 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 per se induce these changes remains to be elucidated.

KW - amino acids

KW - glucagon

KW - humans

KW - non-alcoholic fatty liver disease

KW - type 2 diabetes mellitus

U2 - 10.1530/EC-23-0161

DO - 10.1530/EC-23-0161

M3 - Journal article

C2 - 37947763

AN - SCOPUS:85179328907

VL - 13

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 1

M1 - e230161

ER -

ID: 377947300