Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells

Research output: Contribution to journalJournal articlepeer-review

Standard

Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells. / Elmelund, Emilie; Galsgaard, Katrine D.; Johansen, Christian D.; Trammell, Samuel A.J.; Bomholt, Anna B.; Winther-Sørensen, Marie; Hunt, Jenna E.; Sørensen, Charlotte M.; Kruse, Thomas; Lau, Jesper F.; Grevengoed, Trisha J.; Holst, Jens J.; Wewer Albrechtsen, Nicolai J.

In: iScience, Vol. 25, No. 11, 105296, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Elmelund, E, Galsgaard, KD, Johansen, CD, Trammell, SAJ, Bomholt, AB, Winther-Sørensen, M, Hunt, JE, Sørensen, CM, Kruse, T, Lau, JF, Grevengoed, TJ, Holst, JJ & Wewer Albrechtsen, NJ 2022, 'Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells', iScience, vol. 25, no. 11, 105296. https://doi.org/10.1016/j.isci.2022.105296

APA

Elmelund, E., Galsgaard, K. D., Johansen, C. D., Trammell, S. A. J., Bomholt, A. B., Winther-Sørensen, M., Hunt, J. E., Sørensen, C. M., Kruse, T., Lau, J. F., Grevengoed, T. J., Holst, J. J., & Wewer Albrechtsen, N. J. (2022). Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells. iScience, 25(11), [105296]. https://doi.org/10.1016/j.isci.2022.105296

Vancouver

Elmelund E, Galsgaard KD, Johansen CD, Trammell SAJ, Bomholt AB, Winther-Sørensen M et al. Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells. iScience. 2022;25(11). 105296. https://doi.org/10.1016/j.isci.2022.105296

Author

Elmelund, Emilie ; Galsgaard, Katrine D. ; Johansen, Christian D. ; Trammell, Samuel A.J. ; Bomholt, Anna B. ; Winther-Sørensen, Marie ; Hunt, Jenna E. ; Sørensen, Charlotte M. ; Kruse, Thomas ; Lau, Jesper F. ; Grevengoed, Trisha J. ; Holst, Jens J. ; Wewer Albrechtsen, Nicolai J. / Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells. In: iScience. 2022 ; Vol. 25, No. 11.

Bibtex

@article{57a1410ea319476bbb6660d999c0b6c5,
title = "Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells",
abstract = "The pancreatic hormone, glucagon, is known to regulate hepatic glucose production, but recent studies suggest that its regulation of hepatic amino metabolism is equally important. Here, we show that chronic glucagon receptor activation with a long-acting glucagon analog increases amino acid catabolism and ureagenesis and causes alpha cell hypoplasia in female mice. Conversely, chronic glucagon receptor inhibition with a glucagon receptor antibody decreases amino acid catabolism and ureagenesis and causes alpha cell hyperplasia and beta cell loss. These effects were associated with the transcriptional regulation of hepatic genes related to amino acid uptake and catabolism and by the non-transcriptional modulation of the rate-limiting ureagenesis enzyme, carbamoyl phosphate synthetase-1. Our results support the importance of glucagon receptor signaling for amino acid homeostasis and pancreatic islet integrity in mice and provide knowledge regarding the long-term consequences of chronic glucagon receptor agonism and antagonism.",
keywords = "Biological sciences, Endocrinology, Transcriptomics",
author = "Emilie Elmelund and Galsgaard, {Katrine D.} and Johansen, {Christian D.} and Trammell, {Samuel A.J.} and Bomholt, {Anna B.} and Marie Winther-S{\o}rensen and Hunt, {Jenna E.} and S{\o}rensen, {Charlotte M.} and Thomas Kruse and Lau, {Jesper F.} and Grevengoed, {Trisha J.} and Holst, {Jens J.} and {Wewer Albrechtsen}, {Nicolai J.}",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
doi = "10.1016/j.isci.2022.105296",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Opposing effects of chronic glucagon receptor agonism and antagonism on amino acids, hepatic gene expression, and alpha cells

AU - Elmelund, Emilie

AU - Galsgaard, Katrine D.

AU - Johansen, Christian D.

AU - Trammell, Samuel A.J.

AU - Bomholt, Anna B.

AU - Winther-Sørensen, Marie

AU - Hunt, Jenna E.

AU - Sørensen, Charlotte M.

AU - Kruse, Thomas

AU - Lau, Jesper F.

AU - Grevengoed, Trisha J.

AU - Holst, Jens J.

AU - Wewer Albrechtsen, Nicolai J.

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2022

Y1 - 2022

N2 - The pancreatic hormone, glucagon, is known to regulate hepatic glucose production, but recent studies suggest that its regulation of hepatic amino metabolism is equally important. Here, we show that chronic glucagon receptor activation with a long-acting glucagon analog increases amino acid catabolism and ureagenesis and causes alpha cell hypoplasia in female mice. Conversely, chronic glucagon receptor inhibition with a glucagon receptor antibody decreases amino acid catabolism and ureagenesis and causes alpha cell hyperplasia and beta cell loss. These effects were associated with the transcriptional regulation of hepatic genes related to amino acid uptake and catabolism and by the non-transcriptional modulation of the rate-limiting ureagenesis enzyme, carbamoyl phosphate synthetase-1. Our results support the importance of glucagon receptor signaling for amino acid homeostasis and pancreatic islet integrity in mice and provide knowledge regarding the long-term consequences of chronic glucagon receptor agonism and antagonism.

AB - The pancreatic hormone, glucagon, is known to regulate hepatic glucose production, but recent studies suggest that its regulation of hepatic amino metabolism is equally important. Here, we show that chronic glucagon receptor activation with a long-acting glucagon analog increases amino acid catabolism and ureagenesis and causes alpha cell hypoplasia in female mice. Conversely, chronic glucagon receptor inhibition with a glucagon receptor antibody decreases amino acid catabolism and ureagenesis and causes alpha cell hyperplasia and beta cell loss. These effects were associated with the transcriptional regulation of hepatic genes related to amino acid uptake and catabolism and by the non-transcriptional modulation of the rate-limiting ureagenesis enzyme, carbamoyl phosphate synthetase-1. Our results support the importance of glucagon receptor signaling for amino acid homeostasis and pancreatic islet integrity in mice and provide knowledge regarding the long-term consequences of chronic glucagon receptor agonism and antagonism.

KW - Biological sciences

KW - Endocrinology

KW - Transcriptomics

U2 - 10.1016/j.isci.2022.105296

DO - 10.1016/j.isci.2022.105296

M3 - Journal article

C2 - 36325048

AN - SCOPUS:85140355202

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 11

M1 - 105296

ER -

ID: 324172688