Short-term treatment with GLP-1 increases pulsatile insulin secretion in Type II diabetes with no effect on orderliness.
OBJECTIVE
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 x kg(-1) x 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).


CONCLUSIONS
Short-term stimulation with GLP-1 jointly increases pulsatile and basal insulin secretion, maintaining but not improving system regularity in Type II diabetic patients.
Juhl
C B
CB
Department of Medicine M (Endocrinology and Diabetes), University Hospital of Aarhus, Denmark.
Schmitz
O
O
Pincus
S
S
Holst
J J
JJ
Veldhuis
J
J
Pørksen
N
N
D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010507:Periodicity; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon