Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

TY - JOUR

T1 - Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

AU - Christensen, Mikkel

AU - Knop, Filip K

AU - Vilsbøll, Tina

AU - Aaboe, Kasper

AU - Holst, Jens Juul

AU - Madsbad, Sten

AU - Krarup, Thure

N1 - Copyright (c) 2010 Elsevier B.V. All rights reserved.

PY - 2010/8/9

Y1 - 2010/8/9

N2 - This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5. g intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4 ± 0.5. mM in the first 90. min (period 1) and raised 1.5 times the fasting values to a mean of 11.1 ± 0.1. mM in the last 90. min (period 2). In randomised order either GIP, GLP-2, or saline were infused intravenously during first 50. min in both periods at rates designed to mimic postprandial hormone responses. The resulting incremental area under curve values of glucagon were in period 1 -38 ± 44 (GIP), 120 ± 48 (GLP-2), and -16 ± 61 (saline) pM×90. min (p=0.087), respectively; and in period 2 -157 ± 76, 135 ± 52, and -77 ± 77. pM×90. min (p=0.019), respectively. Post hoc analysis showed significant differences only between the GLP-2 days versus the GIP and saline days. In conclusion, GLP-2, but not GIP, was found to stimulate the release of glucagon in patients with T1DM, suggesting a role for GLP-2 in the postprandial hyperglucagonaemia characterising individuals with T1DM.

AB - This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5. g intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4 ± 0.5. mM in the first 90. min (period 1) and raised 1.5 times the fasting values to a mean of 11.1 ± 0.1. mM in the last 90. min (period 2). In randomised order either GIP, GLP-2, or saline were infused intravenously during first 50. min in both periods at rates designed to mimic postprandial hormone responses. The resulting incremental area under curve values of glucagon were in period 1 -38 ± 44 (GIP), 120 ± 48 (GLP-2), and -16 ± 61 (saline) pM×90. min (p=0.087), respectively; and in period 2 -157 ± 76, 135 ± 52, and -77 ± 77. pM×90. min (p=0.019), respectively. Post hoc analysis showed significant differences only between the GLP-2 days versus the GIP and saline days. In conclusion, GLP-2, but not GIP, was found to stimulate the release of glucagon in patients with T1DM, suggesting a role for GLP-2 in the postprandial hyperglucagonaemia characterising individuals with T1DM.

KW - Adult

KW - Diabetes Mellitus, Type 1

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptide 2

KW - Humans

KW - Time Factors

KW - Young Adult

U2 - 10.1016/j.regpep.2010.05.004

DO - 10.1016/j.regpep.2010.05.004

M3 - Journal article

C2 - 20580750

SN - 0167-0115

VL - 163

SP - 96

EP - 101

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 1-3

ER -