Aims/hypothesis. The enteric incretin hormone, glucagon-like peptide-1 (GLP-1), is a potent insulin secretagogue in healthy humans and patients
with Type II (non-insulin-dependent) diabetes mellitus. In this study we assessed the impact of short-term GLP-1 infusion
on pulsatile insulin secretion in Type II diabetic patients.
Methods. Type II diabetic patients (
n = 8) were studied in a randomised cross-over design. Plasma insulin concentration time series were obtained during basal
conditions and during infusion with saline or GLP-1 (1.2 pmol/l · kg
–1· min
–1) on 2 separate days. Plasma glucose was clamped at the initial concentration by a variable glucose infusion. Serum insulin
concentration time series were evaluated by deconvolution analysis, autocorrelation analysis, spectral analysis and approximate
entropy.
Results. Serum insulin concentrations increased by approximately 100 % during GLP-1 infusion. Pulsatile insulin secretion was increased
as measured by secretory burst mass (19.3 ± 3.8 vs 53.0 ± 10.7 pmol/l/pulse,
p = 0.02) and secretory burst amplitude (7.7 ± 1.5 vs 21.1 ± 4.3 pmol/l/min,
p = 0.02). A similar increase in basal insulin secretion was observed (3.6 ± 0.9 vs 10.2 ± 2.2 pmol/l/min,
p = 0.004) with no changes in the fraction of insulin delivered in pulses (0.50 ± 0.06 vs 0.49 ± 0.02,
p = 0.84). Regularity of secretion was unchanged as measured by spectral analysis (normalised spectral power: 5.9 ± 0.6 vs
6.3 ± 0.8,
p = 0.86), autocorrelation analysis (autocorrelation coefficient: 0.19 ± 0.04 vs 0.18 ± 0.05,
p = 0.66) and the approximate entropy statistic (1.48 ± 0.02 vs 1.51 ± 0.02,
p = 0.86).
Conclusion/interpretation. Short-term stimulation with GLP-1 jointly increases pulsatile and basal insulin secretion, maintaining but not improving
system regularity in Type II diabetic patients. [Diabetologia (2000) 43: 583–588]
Keywords GLP-1 - Insulin - pulsatility - insulin secretion - time series - Type II diabetes - human.
Received: 11 November 1999 and in revised form: 13 December 1999