Glucagon-like peptide 1 (GLP-1) is a
peptide hormone that is released from the gut after
luminal stimulation. The
hormone is a potent
insulin secretagogue and is a potential novel
pharmaceutical adjuvant in the treatment of
NIDDM.
Insulin is secreted as a series of punctuated secretory bursts superimposed on a basal
insulin release. Recently, the contribution of these secretory bursts to overall insulin secretion has been evaluated, and studies using catheterization across the pancreas in a canine model and studies using deconvolution in humans have revealed that the majority of
insulin is released during these secretory bursts. Moreover, the main regulation of insulin secretion is through perturbation of mass and frequency of these secretory bursts. The mode of delivery of
insulin into the circulation seems important for
insulin action, and it is therefore important to know the impact of a potential therapeutic
insulin secretagogue on the mode of insulin secretion. To assess the effects of
GLP-1 on the mass, frequency, amplitude, and overall contribution of pulsatile insulin secretion, we used a recently validated deconvolution model to examine these variables before and during infusion of
GLP-1 in eight healthy men (age 28 +/- 2 years; BMI 24 +/- 2 kg/m2). At a constant
glucose infusion (2.5 mg x kg-1 x min-1), near-steady state was reached at 75 min, and sampling was performed every minute at t = 75-115 and 145-185 min. At t = 115 min, an infusion of saline or
GLP-1 (50 pmol x kg-1 x min-1) was given. The regularity of insulin secretion was measured by approximate entropy, a recently developed mathematical statistic, applied herein to assess the regularity in a
hormone concentration time series. After
GLP-1 infusion, there was an abrupt increase in the peripheral concentrations of serum
C-peptide (696 +/- 65 vs. 1,538 +/- 165 pmol/l) and
insulin (49 +/- 8 vs. 138 +/- 21 pmol/l) concentrations. This increase was mainly due to an increase in the pulsatile component of insulin secretion that was achieved by a fourfold increase in secretory burst mass (28.2 +/- 4.4 vs. 100.1 +/- 15.8 pmol x l-1 x pulse-1; P < 0.001), and amplitude (12.7 +/- 2.2 vs. 4.3 +/- 7.7 pmol x l-1 x min-1; P < 0.002), whereas the secretory burst frequency was not affected by
GLP-1 (11.5 +/- 0.7 vs. 12.6 +/- 0.6 pulses/h; P = 0.4). As a consequence, the detected contribution of pulsatile to overall insulin secretion was increased from 56 +/- 4 to 77 +/- 4% (P < 0.005). The orderliness of the
insulin release process was not deteriorated by short-term
GLP-1 infusion as assessed by approximate entropy (1.19 +/- 0.04 vs. 1.18 +/- 0.04; P = 0.7).