Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis. / Suppli, Malte P.; Bagger, Jonatan I.; Lund, Asger; Demant, Mia; van Hall, Gerrit; Strandberg, Charlotte; Kønig, Merete J.; Rigbolt, Kristoffer; Langhoff, Jill L.; Wewer Albrechtsen, Nicolai J.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.

In: Diabetes, Vol. 69, No. 6, 2020, p. 1090-1099.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Suppli, MP, Bagger, JI, Lund, A, Demant, M, van Hall, G, Strandberg, C, Kønig, MJ, Rigbolt, K, Langhoff, JL, Wewer Albrechtsen, NJ, Holst, JJ, Vilsbøll, T & Knop, FK 2020, 'Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis', Diabetes, vol. 69, no. 6, pp. 1090-1099. https://doi.org/10.2337/db19-0715

APA

Suppli, M. P., Bagger, J. I., Lund, A., Demant, M., van Hall, G., Strandberg, C., Kønig, M. J., Rigbolt, K., Langhoff, J. L., Wewer Albrechtsen, N. J., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2020). Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis. Diabetes, 69(6), 1090-1099. https://doi.org/10.2337/db19-0715

Vancouver

Suppli MP, Bagger JI, Lund A, Demant M, van Hall G, Strandberg C et al. Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis. Diabetes. 2020;69(6):1090-1099. https://doi.org/10.2337/db19-0715

Author

Suppli, Malte P. ; Bagger, Jonatan I. ; Lund, Asger ; Demant, Mia ; van Hall, Gerrit ; Strandberg, Charlotte ; Kønig, Merete J. ; Rigbolt, Kristoffer ; Langhoff, Jill L. ; Wewer Albrechtsen, Nicolai J. ; Holst, Jens J. ; Vilsbøll, Tina ; Knop, Filip K. / Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis. In: Diabetes. 2020 ; Vol. 69, No. 6. pp. 1090-1099.

Bibtex

@article{aafe980133074c9ba7cde7ff1cc03f16,
title = "Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis",
abstract = "Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role and that hepatic amino acid metabolism and glucagon are linked in a mutual feedback cycle, the liver-α-cell axis. On the basis of this knowledge, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia. We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals. Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.",
author = "Suppli, {Malte P.} and Bagger, {Jonatan I.} and Asger Lund and Mia Demant and {van Hall}, Gerrit and Charlotte Strandberg and K{\o}nig, {Merete J.} and Kristoffer Rigbolt and Langhoff, {Jill L.} and {Wewer Albrechtsen}, {Nicolai J.} and Holst, {Jens J.} and Tina Vilsb{\o}ll and Knop, {Filip K.}",
year = "2020",
doi = "10.2337/db19-0715",
language = "English",
volume = "69",
pages = "1090--1099",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

RIS

TY - JOUR

T1 - Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis

AU - Suppli, Malte P.

AU - Bagger, Jonatan I.

AU - Lund, Asger

AU - Demant, Mia

AU - van Hall, Gerrit

AU - Strandberg, Charlotte

AU - Kønig, Merete J.

AU - Rigbolt, Kristoffer

AU - Langhoff, Jill L.

AU - Wewer Albrechtsen, Nicolai J.

AU - Holst, Jens J.

AU - Vilsbøll, Tina

AU - Knop, Filip K.

PY - 2020

Y1 - 2020

N2 - Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role and that hepatic amino acid metabolism and glucagon are linked in a mutual feedback cycle, the liver-α-cell axis. On the basis of this knowledge, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia. We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals. Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.

AB - Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role and that hepatic amino acid metabolism and glucagon are linked in a mutual feedback cycle, the liver-α-cell axis. On the basis of this knowledge, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia. We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals. Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.

U2 - 10.2337/db19-0715

DO - 10.2337/db19-0715

M3 - Journal article

C2 - 31974144

AN - SCOPUS:85085233227

VL - 69

SP - 1090

EP - 1099

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

ID: 244531289