Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus

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Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. / Hare, Kristine J; Knop, Filip K; Asmar, Meena; Madsbad, Sten; Deacon, Carolyn F; Holst, Jens J; Vilsbøll, Tina.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 12, 2009, p. 4679-87.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hare, KJ, Knop, FK, Asmar, M, Madsbad, S, Deacon, CF, Holst, JJ & Vilsbøll, T 2009, 'Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 12, pp. 4679-87. https://doi.org/10.1210/jc.2009-0921

APA

Hare, K. J., Knop, F. K., Asmar, M., Madsbad, S., Deacon, C. F., Holst, J. J., & Vilsbøll, T. (2009). Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism, 94(12), 4679-87. https://doi.org/10.1210/jc.2009-0921

Vancouver

Hare KJ, Knop FK, Asmar M, Madsbad S, Deacon CF, Holst JJ et al. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism. 2009;94(12):4679-87. https://doi.org/10.1210/jc.2009-0921

Author

Hare, Kristine J ; Knop, Filip K ; Asmar, Meena ; Madsbad, Sten ; Deacon, Carolyn F ; Holst, Jens J ; Vilsbøll, Tina. / Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 12. pp. 4679-87.

Bibtex

@article{233687e0332f11df8ed1000ea68e967b,
title = "Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus",
abstract = "OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is insulinotropic, but its effect on the alpha-cell is less clear. We investigated the dose-response relationship for GLP-1-induced glucagon suppression in patients with type 2 diabetes (T2DM) and healthy controls. DESIGN: Ten patients with T2DM (duration of DM, 4 +/- 1 yr; glycosylated hemoglobin, 7.1 +/- 0.3{\%}) were studied on 2 d, with stepwise increasing GLP-1 infusions (0.25, 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1)) (d 1) or saline (d 2) with plasma glucose (PG) clamped at fasting level. On d 3, patient PG was normalized overnight using a variable insulin infusion, followed by a 3-h GLP-1 infusion as on d 1. Ten healthy subjects were examined with the same protocol on d 1 and 2. RESULTS: We observed similar dose-dependent stepwise suppression of glucagon secretion in both patients and controls. Significant suppression was observed at a GLP-1 infusion rate of 0.25 pmol x kg(-1) x min(-1) (resulting in physiological plasma concentrations) as early as time 15 min in healthy controls and time 30 min in patients (d 1 and d 3). AUC for glucagon was significantly reduced on d 1 and 3 (1096 +/- 109 and 1116 +/- 108 3h x pmol/liter; P = NS) as compared to d 2 (1733 +/- 193 3h x pmol/liter; P < 0.01) in patients with T2DM. A similar reduction in AUC for glucagon was observed in healthy controls [1122 +/- 186 (d 1) vs. 1733 +/- 312 3h x pmol/liter (d 2); P < 0.001]. CONCLUSIONS: The diabetic alpha-cell appears to be highly sensitive to the inhibitory action of GLP-1 both during high and near-normalized PG levels, but responds with a short, nevertheless significant delay.",
author = "Hare, {Kristine J} and Knop, {Filip K} and Meena Asmar and Sten Madsbad and Deacon, {Carolyn F} and Holst, {Jens J} and Tina Vilsb{\o}ll",
note = "Keywords: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged",
year = "2009",
doi = "10.1210/jc.2009-0921",
language = "English",
volume = "94",
pages = "4679--87",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus

AU - Hare, Kristine J

AU - Knop, Filip K

AU - Asmar, Meena

AU - Madsbad, Sten

AU - Deacon, Carolyn F

AU - Holst, Jens J

AU - Vilsbøll, Tina

N1 - Keywords: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Secreting Cells; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged

PY - 2009

Y1 - 2009

N2 - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is insulinotropic, but its effect on the alpha-cell is less clear. We investigated the dose-response relationship for GLP-1-induced glucagon suppression in patients with type 2 diabetes (T2DM) and healthy controls. DESIGN: Ten patients with T2DM (duration of DM, 4 +/- 1 yr; glycosylated hemoglobin, 7.1 +/- 0.3%) were studied on 2 d, with stepwise increasing GLP-1 infusions (0.25, 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1)) (d 1) or saline (d 2) with plasma glucose (PG) clamped at fasting level. On d 3, patient PG was normalized overnight using a variable insulin infusion, followed by a 3-h GLP-1 infusion as on d 1. Ten healthy subjects were examined with the same protocol on d 1 and 2. RESULTS: We observed similar dose-dependent stepwise suppression of glucagon secretion in both patients and controls. Significant suppression was observed at a GLP-1 infusion rate of 0.25 pmol x kg(-1) x min(-1) (resulting in physiological plasma concentrations) as early as time 15 min in healthy controls and time 30 min in patients (d 1 and d 3). AUC for glucagon was significantly reduced on d 1 and 3 (1096 +/- 109 and 1116 +/- 108 3h x pmol/liter; P = NS) as compared to d 2 (1733 +/- 193 3h x pmol/liter; P < 0.01) in patients with T2DM. A similar reduction in AUC for glucagon was observed in healthy controls [1122 +/- 186 (d 1) vs. 1733 +/- 312 3h x pmol/liter (d 2); P < 0.001]. CONCLUSIONS: The diabetic alpha-cell appears to be highly sensitive to the inhibitory action of GLP-1 both during high and near-normalized PG levels, but responds with a short, nevertheless significant delay.

AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is insulinotropic, but its effect on the alpha-cell is less clear. We investigated the dose-response relationship for GLP-1-induced glucagon suppression in patients with type 2 diabetes (T2DM) and healthy controls. DESIGN: Ten patients with T2DM (duration of DM, 4 +/- 1 yr; glycosylated hemoglobin, 7.1 +/- 0.3%) were studied on 2 d, with stepwise increasing GLP-1 infusions (0.25, 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1)) (d 1) or saline (d 2) with plasma glucose (PG) clamped at fasting level. On d 3, patient PG was normalized overnight using a variable insulin infusion, followed by a 3-h GLP-1 infusion as on d 1. Ten healthy subjects were examined with the same protocol on d 1 and 2. RESULTS: We observed similar dose-dependent stepwise suppression of glucagon secretion in both patients and controls. Significant suppression was observed at a GLP-1 infusion rate of 0.25 pmol x kg(-1) x min(-1) (resulting in physiological plasma concentrations) as early as time 15 min in healthy controls and time 30 min in patients (d 1 and d 3). AUC for glucagon was significantly reduced on d 1 and 3 (1096 +/- 109 and 1116 +/- 108 3h x pmol/liter; P = NS) as compared to d 2 (1733 +/- 193 3h x pmol/liter; P < 0.01) in patients with T2DM. A similar reduction in AUC for glucagon was observed in healthy controls [1122 +/- 186 (d 1) vs. 1733 +/- 312 3h x pmol/liter (d 2); P < 0.001]. CONCLUSIONS: The diabetic alpha-cell appears to be highly sensitive to the inhibitory action of GLP-1 both during high and near-normalized PG levels, but responds with a short, nevertheless significant delay.

U2 - 10.1210/jc.2009-0921

DO - 10.1210/jc.2009-0921

M3 - Journal article

C2 - 19837930

VL - 94

SP - 4679

EP - 4687

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -

ID: 18697592