The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects
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The influence of GLP-1 on glucose-stimulated insulin secretion : effects on beta-cell sensitivity in type 2 and nondiabetic subjects. / Kjems, Lise L; Holst, Jens Juul; Vølund, Aage; Madsbad, Sten.
In: Diabetes, Vol. 52, No. 2, 02.2003, p. 380-6.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The influence of GLP-1 on glucose-stimulated insulin secretion
T2 - effects on beta-cell sensitivity in type 2 and nondiabetic subjects
AU - Kjems, Lise L
AU - Holst, Jens Juul
AU - Vølund, Aage
AU - Madsbad, Sten
PY - 2003/2
Y1 - 2003/2
N2 - The intestinally derived hormone glucagon-like peptide 1 (GLP-1) (7-36 amide) has potent effects on glucose-mediated insulin secretion, insulin gene expression, and beta-cell growth and differentiation. It is, therefore, considered a potential therapeutic agent for the treatment of type 2 diabetes. However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2, 4, 6, 8, and 12 mg x kg(-1) x min(-1) over 150 min on four occasions with infusion of saline or GLP-1 at 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1). GLP-1 enhanced ISR in a dose-dependent manner during the graded glucose infusion from 332 +/- 51 to 975 +/- 198 pmol/kg in the patients with type 2 diabetes and from 711 +/- 123 to 2,415 +/- 243 pmol/kg in the control subjects. The beta-cell responsiveness to glucose, expressed as the slope of the linear relation between ISR and the glucose concentration, increased in proportion to the GLP-1 dose to 6 times relative to saline at the highest GLP-1 dose in the patients and 11 times in the control subjects, but it was 3 to 5 times lower in the patients with type 2 diabetes compared with healthy subjects at the same GLP-1 dose. During infusion of GLP-1 at 0.5 pmol x kg(-1) x min(-1) in the patients, the slope of ISR versus glucose became indistinguishable from that of the control subjects without GLP-1. Our results show that GLP-1 increases insulin secretion in patients with type 2 diabetes and control subjects in a dose-dependent manner and that the beta-cell responsiveness to glucose may be increased to normal levels with a low dose of GLP-1 infusion. Nevertheless, the results also indicate that the dose-response relation between beta-cell responsiveness to glucose and GLP-1 is severely impaired in patients with type 2 diabetes.
AB - The intestinally derived hormone glucagon-like peptide 1 (GLP-1) (7-36 amide) has potent effects on glucose-mediated insulin secretion, insulin gene expression, and beta-cell growth and differentiation. It is, therefore, considered a potential therapeutic agent for the treatment of type 2 diabetes. However, the dose-response relationship between GLP-1 and basal and glucose-stimulated prehepatic insulin secretion rate (ISR) is currently not known. Seven patients with type 2 diabetes and seven matched nondiabetic control subjects were studied. ISR was determined during a graded glucose infusion of 2, 4, 6, 8, and 12 mg x kg(-1) x min(-1) over 150 min on four occasions with infusion of saline or GLP-1 at 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1). GLP-1 enhanced ISR in a dose-dependent manner during the graded glucose infusion from 332 +/- 51 to 975 +/- 198 pmol/kg in the patients with type 2 diabetes and from 711 +/- 123 to 2,415 +/- 243 pmol/kg in the control subjects. The beta-cell responsiveness to glucose, expressed as the slope of the linear relation between ISR and the glucose concentration, increased in proportion to the GLP-1 dose to 6 times relative to saline at the highest GLP-1 dose in the patients and 11 times in the control subjects, but it was 3 to 5 times lower in the patients with type 2 diabetes compared with healthy subjects at the same GLP-1 dose. During infusion of GLP-1 at 0.5 pmol x kg(-1) x min(-1) in the patients, the slope of ISR versus glucose became indistinguishable from that of the control subjects without GLP-1. Our results show that GLP-1 increases insulin secretion in patients with type 2 diabetes and control subjects in a dose-dependent manner and that the beta-cell responsiveness to glucose may be increased to normal levels with a low dose of GLP-1 infusion. Nevertheless, the results also indicate that the dose-response relation between beta-cell responsiveness to glucose and GLP-1 is severely impaired in patients with type 2 diabetes.
KW - Area Under Curve
KW - Blood Glucose
KW - C-Peptide
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Glucose Clamp Technique
KW - Humans
KW - Infusions, Intravenous
KW - Insulin
KW - Islets of Langerhans
KW - Kinetics
KW - Male
KW - Peptide Fragments
KW - Protein Precursors
KW - Reference Values
M3 - Journal article
C2 - 12540611
VL - 52
SP - 380
EP - 386
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 2
ER -
ID: 132056313