Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure

Jonatan I Bagger; Jens J Holst; Bolette Hartmann; Birgitte Andersen; Filip K Knop; Tina Vilsbøll

doi:10.1210/jc.2015-2335

Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure

Jonatan I Bagger, Jens J Holst, Bolette Hartmann, Birgitte Andersen, Filip K Knop, Tina Vilsbøll

Endocrinology and Metabolism

48 Citationer (Scopus)

Abstract

Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective:Wewantedto delineate the contributions of separateandcombinedGLP-1 receptorand glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin. Design: This was a double-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m²; fasting plasma glucose 5.1 [4.4 -5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol). Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg^-1 × min^-1), glucagon (0.86 pmol × kg^-1 × min^-1), oxyntomodulin (3 pmol × kg^-1 × min^-1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1+ glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.

Originalsprog	Engelsk
Tidsskrift	The Journal of Clinical Endocrinology & Metabolism
Vol/bind	100
Udgave nummer	12
Sider (fra-til)	4541–4552
Antal sider	12
ISSN	0021-972X
DOI	https://doi.org/10.1210/jc.2015-2335
Status	Udgivet - dec. 2015

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10.1210/jc.2015-2335

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Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure. / Bagger, Jonatan I; Holst, Jens J ; Hartmann, Bolette et al.

I: The Journal of Clinical Endocrinology & Metabolism, Bind 100, Nr. 12, 12.2015, s. 4541–4552.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{96760698f2bc4f7a81d357e6ced9483c,

title = "Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure",

abstract = "Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective:Wewantedto delineate the contributions of separateandcombinedGLP-1 receptorand glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin. Design: This was a double-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m2; fasting plasma glucose 5.1 [4.4 -5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol). Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg-1 × min-1), glucagon (0.86 pmol × kg-1 × min-1), oxyntomodulin (3 pmol × kg-1 × min-1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1+ glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.",

author = "Bagger, {Jonatan I} and Holst, {Jens J} and Bolette Hartmann and Birgitte Andersen and Knop, {Filip K} and Tina Vilsb{\o}ll",

year = "2015",

month = dec,

doi = "10.1210/jc.2015-2335",

language = "English",

volume = "100",

pages = "4541–4552",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "12",

}

TY - JOUR

T1 - Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure

AU - Bagger, Jonatan I

AU - Holst, Jens J

AU - Hartmann, Bolette

AU - Andersen, Birgitte

AU - Knop, Filip K

AU - Vilsbøll, Tina

PY - 2015/12

Y1 - 2015/12

N2 - Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective:Wewantedto delineate the contributions of separateandcombinedGLP-1 receptorand glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin. Design: This was a double-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m2; fasting plasma glucose 5.1 [4.4 -5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol). Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg-1 × min-1), glucagon (0.86 pmol × kg-1 × min-1), oxyntomodulin (3 pmol × kg-1 × min-1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1+ glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.

AB - Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective:Wewantedto delineate the contributions of separateandcombinedGLP-1 receptorand glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin. Design: This was a double-blinded, randomized, crossover study. Setting: The study was conducted at a specialized research unit. Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m2; fasting plasma glucose 5.1 [4.4 -5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol). Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol × kg-1 × min-1), glucagon (0.86 pmol × kg-1 × min-1), oxyntomodulin (3 pmol × kg-1 × min-1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1+ glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.

U2 - 10.1210/jc.2015-2335

DO - 10.1210/jc.2015-2335

M3 - Journal article

C2 - 26445112

SN - 0021-972X

VL - 100

SP - 4541

EP - 4552

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 12

ER -

Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure

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