On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA

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

Standard

On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA. / Wewer Albrechtsen, Nicolai J.; Kjeldsen, Sasha A. S.; Jensen, Nicole J.; Rungby, Jørgen; Veedfald, Simon; Bojsen-Møller, Kirstine N.; Dirksen, Carsten; Jensen, Christian Z.; Martinussen, Christoffer; Madsbad, Sten; Holst, Jens J.

In: Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 82, No. 1, 2022, p. 75-83.

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

Harvard

Wewer Albrechtsen, NJ, Kjeldsen, SAS, Jensen, NJ, Rungby, J, Veedfald, S, Bojsen-Møller, KN, Dirksen, C, Jensen, CZ, Martinussen, C, Madsbad, S & Holst, JJ 2022, 'On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA', Scandinavian Journal of Clinical & Laboratory Investigation, vol. 82, no. 1, pp. 75-83. https://doi.org/10.1080/00365513.2021.2016943

APA

Wewer Albrechtsen, N. J., Kjeldsen, S. A. S., Jensen, N. J., Rungby, J., Veedfald, S., Bojsen-Møller, K. N., Dirksen, C., Jensen, C. Z., Martinussen, C., Madsbad, S., & Holst, J. J. (2022). On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA. Scandinavian Journal of Clinical & Laboratory Investigation, 82(1), 75-83. https://doi.org/10.1080/00365513.2021.2016943

Vancouver

Wewer Albrechtsen NJ, Kjeldsen SAS, Jensen NJ, Rungby J, Veedfald S, Bojsen-Møller KN et al. On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA. Scandinavian Journal of Clinical & Laboratory Investigation. 2022;82(1):75-83. https://doi.org/10.1080/00365513.2021.2016943

Author

Wewer Albrechtsen, Nicolai J. ; Kjeldsen, Sasha A. S. ; Jensen, Nicole J. ; Rungby, Jørgen ; Veedfald, Simon ; Bojsen-Møller, Kirstine N. ; Dirksen, Carsten ; Jensen, Christian Z. ; Martinussen, Christoffer ; Madsbad, Sten ; Holst, Jens J. / On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA. In: Scandinavian Journal of Clinical & Laboratory Investigation. 2022 ; Vol. 82, No. 1. pp. 75-83.

Bibtex

@article{3c8331a444ba4400958c88fb54f4ec06,
title = "On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA",
abstract = "Glucagon is a key regulator of metabolism and is used in the diagnostic of neuroendocrine tumors. Accurate measurement of glucagon requires both extreme sensitivity and specificity since several peptides are derived from the same proglucagon precursor encoding part of the glucagon sequence and given that glucagon circulates in picomolar concentrations. A sandwich ELISA was recently developed and extensively evaluated; however, this method may not be accurate when measuring glucagon in patients with an enhanced production of proglucagon-derived peptides as seen after Roux-en-Y gastric bypass (RYGB). To overcome this, a modified version of the ELISA was developed. In this study, we evaluate an unmodified and a modified version of the ELISA in healthy individuals, individuals with obesity, and finally in two cohorts of patients following RYGB surgery using different nutrient stimuli to assess glucagon dynamics. Finally, in vitro spike-in recoveries using native glucagon and proglucagon-derived peptides were performed in buffer and in plasma. Our data support that both versions of the ELISA accurately capture endogenous and exogenous glucagon in healthy individuals and in individuals with obesity. However, the unmodified version of the assay may overestimate glucagon levels in patients following RYGB in line with minimal but consistent cross-reactivity to oxyntomodulin and glicentin that both are 50-fold increased after RYGB. Importantly, we did not find any changes between the two protocols at fasted conditions and therefore diagnostics of glucagonomas is not affected by the choice of assay procedure nor the surgical history of the patient (RYGB).",
keywords = "ELISA, glicentin, glucagon, metabolism, oxyntomodulin, RYGB",
author = "{Wewer Albrechtsen}, {Nicolai J.} and Kjeldsen, {Sasha A. S.} and Jensen, {Nicole J.} and J{\o}rgen Rungby and Simon Veedfald and Bojsen-M{\o}ller, {Kirstine N.} and Carsten Dirksen and Jensen, {Christian Z.} and Christoffer Martinussen and Sten Madsbad and Holst, {Jens J.}",
year = "2022",
doi = "10.1080/00365513.2021.2016943",
language = "English",
volume = "82",
pages = "75--83",
journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
issn = "0036-5513",
publisher = "Taylor & Francis",
number = "1",

}

RIS

TY - JOUR

T1 - On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA

AU - Wewer Albrechtsen, Nicolai J.

AU - Kjeldsen, Sasha A. S.

AU - Jensen, Nicole J.

AU - Rungby, Jørgen

AU - Veedfald, Simon

AU - Bojsen-Møller, Kirstine N.

AU - Dirksen, Carsten

AU - Jensen, Christian Z.

AU - Martinussen, Christoffer

AU - Madsbad, Sten

AU - Holst, Jens J.

PY - 2022

Y1 - 2022

N2 - Glucagon is a key regulator of metabolism and is used in the diagnostic of neuroendocrine tumors. Accurate measurement of glucagon requires both extreme sensitivity and specificity since several peptides are derived from the same proglucagon precursor encoding part of the glucagon sequence and given that glucagon circulates in picomolar concentrations. A sandwich ELISA was recently developed and extensively evaluated; however, this method may not be accurate when measuring glucagon in patients with an enhanced production of proglucagon-derived peptides as seen after Roux-en-Y gastric bypass (RYGB). To overcome this, a modified version of the ELISA was developed. In this study, we evaluate an unmodified and a modified version of the ELISA in healthy individuals, individuals with obesity, and finally in two cohorts of patients following RYGB surgery using different nutrient stimuli to assess glucagon dynamics. Finally, in vitro spike-in recoveries using native glucagon and proglucagon-derived peptides were performed in buffer and in plasma. Our data support that both versions of the ELISA accurately capture endogenous and exogenous glucagon in healthy individuals and in individuals with obesity. However, the unmodified version of the assay may overestimate glucagon levels in patients following RYGB in line with minimal but consistent cross-reactivity to oxyntomodulin and glicentin that both are 50-fold increased after RYGB. Importantly, we did not find any changes between the two protocols at fasted conditions and therefore diagnostics of glucagonomas is not affected by the choice of assay procedure nor the surgical history of the patient (RYGB).

AB - Glucagon is a key regulator of metabolism and is used in the diagnostic of neuroendocrine tumors. Accurate measurement of glucagon requires both extreme sensitivity and specificity since several peptides are derived from the same proglucagon precursor encoding part of the glucagon sequence and given that glucagon circulates in picomolar concentrations. A sandwich ELISA was recently developed and extensively evaluated; however, this method may not be accurate when measuring glucagon in patients with an enhanced production of proglucagon-derived peptides as seen after Roux-en-Y gastric bypass (RYGB). To overcome this, a modified version of the ELISA was developed. In this study, we evaluate an unmodified and a modified version of the ELISA in healthy individuals, individuals with obesity, and finally in two cohorts of patients following RYGB surgery using different nutrient stimuli to assess glucagon dynamics. Finally, in vitro spike-in recoveries using native glucagon and proglucagon-derived peptides were performed in buffer and in plasma. Our data support that both versions of the ELISA accurately capture endogenous and exogenous glucagon in healthy individuals and in individuals with obesity. However, the unmodified version of the assay may overestimate glucagon levels in patients following RYGB in line with minimal but consistent cross-reactivity to oxyntomodulin and glicentin that both are 50-fold increased after RYGB. Importantly, we did not find any changes between the two protocols at fasted conditions and therefore diagnostics of glucagonomas is not affected by the choice of assay procedure nor the surgical history of the patient (RYGB).

KW - ELISA

KW - glicentin

KW - glucagon

KW - metabolism

KW - oxyntomodulin

KW - RYGB

U2 - 10.1080/00365513.2021.2016943

DO - 10.1080/00365513.2021.2016943

M3 - Journal article

C2 - 34935574

VL - 82

SP - 75

EP - 83

JO - Scandinavian Journal of Clinical & Laboratory Investigation

JF - Scandinavian Journal of Clinical & Laboratory Investigation

SN - 0036-5513

IS - 1

ER -

ID: 288272668