Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans

TY - JOUR

T1 - Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans

AU - Ahrén, Bo

AU - Holst, Jens Juul

AU - Mari, Andrea

PY - 2003/10

Y1 - 2003/10

N2 - OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its beta-cell effects are important to establish. Previously, beta-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known.RESEARCH DESIGN AND METHODS: Eight women (aged 69 years, fasting glucose 3.7-10.3 mmol/l, BMI 22.4-43.9 kg/m(2)) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol x kg(-1) x min(-1)), and beta-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data).RESULTS: -GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 +/- 4.2 nmol/m(2) with GLP-1 versus 21.0 +/- 1.6 nmol/m(2) with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 +/- 26 with GLP-1 versus 38 +/- 16 pmol insulin. min(-1 x m(2). mmol(-1) glucose. l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 +/- 0.42 with GLP-1 versus 0.97 +/- 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI.CONCLUSIONS: Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.

AB - OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its beta-cell effects are important to establish. Previously, beta-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known.RESEARCH DESIGN AND METHODS: Eight women (aged 69 years, fasting glucose 3.7-10.3 mmol/l, BMI 22.4-43.9 kg/m(2)) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol x kg(-1) x min(-1)), and beta-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data).RESULTS: -GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 +/- 4.2 nmol/m(2) with GLP-1 versus 21.0 +/- 1.6 nmol/m(2) with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 +/- 26 with GLP-1 versus 38 +/- 16 pmol insulin. min(-1 x m(2). mmol(-1) glucose. l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 +/- 0.42 with GLP-1 versus 0.97 +/- 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI.CONCLUSIONS: Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.

KW - Aged

KW - Blood Glucose

KW - C-Peptide

KW - Eating

KW - Female

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Peptide Fragments

KW - Postprandial Period

KW - Protein Precursors

M3 - Journal article

C2 - 14514592

SN - 1935-5548

VL - 26

SP - 2860

EP - 2864

JO - Diabetes Care

JF - Diabetes Care

IS - 10

ER -