Impact of exogenous hyperglucagonemia on postprandial concentrations of gastric inhibitory polypeptide and glucagon-like peptide-1 in humans

TY - JOUR

T1 - Impact of exogenous hyperglucagonemia on postprandial concentrations of gastric inhibitory polypeptide and glucagon-like peptide-1 in humans

AU - Meier, Juris J

AU - Ritter, Peter R

AU - Jacob, Alexandra

AU - Menge, Bjoern A

AU - Deacon, Carolyn F

AU - Schmidt, Wolfgang E

AU - Nauck, Michael A

AU - Holst, Jens J

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Background: Postprandial secretion of glucagon-like peptide 1 (GLP-1) has been found diminished in some patients with type 2 diabetes mellitus (T2DM) and high glucagon concentrations. We examined the effects of exogenous glucagon on the release of incretin hormones. Patients and Methods: Ten patients with T2DM and 10 healthy controls were examined with a meal test during the iv administration of glucagon 0.65 ng/kg · min and placebo. Results: GLP-1 plasma concentration increased after meal ingestion in both groups (P < 0.0001), but postprandial GLP-1 plasma levels were not affected by glucagon administration. However, immediately after cessation of the glucagon infusion, GLP-1 levels increased by about 2-fold to levels of 51.8 ± 14.6 pmol/liter in the T2DM patients and 58.9 ± 20.0 pmol/liter in controls (P < 0.05). The time courses of glucose-dependent insulinotropic peptide glucose-dependent insulinotropic peptide and GLP-1 concentrations were not different between T2DM patients and controls during the placebo experiments (P = 0.33 and P = 0.13, respectively). Glucose concentrations were increased by glucagon administration in controls (P < 0.05, respectively), but insulin and C-peptide levels were not affected. Gastric emptying was slightly delayed by glucagon administration in controls (P < 0.05) but not in T2DM patients (P = 0.77). Conclusions: Exogenous glucagon does not directly inhibit incretin secretion. However, a decline in circulating glucagon levels may exert a permissive effect on GLP-1 release. This might contribute to the reduction in GLP-1 concentrations found in some patients with T2DM.

AB - Background: Postprandial secretion of glucagon-like peptide 1 (GLP-1) has been found diminished in some patients with type 2 diabetes mellitus (T2DM) and high glucagon concentrations. We examined the effects of exogenous glucagon on the release of incretin hormones. Patients and Methods: Ten patients with T2DM and 10 healthy controls were examined with a meal test during the iv administration of glucagon 0.65 ng/kg · min and placebo. Results: GLP-1 plasma concentration increased after meal ingestion in both groups (P < 0.0001), but postprandial GLP-1 plasma levels were not affected by glucagon administration. However, immediately after cessation of the glucagon infusion, GLP-1 levels increased by about 2-fold to levels of 51.8 ± 14.6 pmol/liter in the T2DM patients and 58.9 ± 20.0 pmol/liter in controls (P < 0.05). The time courses of glucose-dependent insulinotropic peptide glucose-dependent insulinotropic peptide and GLP-1 concentrations were not different between T2DM patients and controls during the placebo experiments (P = 0.33 and P = 0.13, respectively). Glucose concentrations were increased by glucagon administration in controls (P < 0.05, respectively), but insulin and C-peptide levels were not affected. Gastric emptying was slightly delayed by glucagon administration in controls (P < 0.05) but not in T2DM patients (P = 0.77). Conclusions: Exogenous glucagon does not directly inhibit incretin secretion. However, a decline in circulating glucagon levels may exert a permissive effect on GLP-1 release. This might contribute to the reduction in GLP-1 concentrations found in some patients with T2DM.

KW - Aged

KW - Analysis of Variance

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Incretins

KW - Insulin

KW - Male

KW - Middle Aged

KW - Postprandial Period

U2 - 10.1210/jc.2010-0550

DO - 10.1210/jc.2010-0550

M3 - Journal article

C2 - 20501678

SN - 0021-972X

VL - 95

SP - 4061

EP - 4065

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -