R. Lugari et al., Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes, HORMONE MET, 32(10), 2000, pp. 424-428
Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2
diabetic patients, resulting the peptide administration in a near-normaliz
ation of plasma glucose mainly through its insulinotropic effect. GLP-1 als
o reduces meal-related insulin requirement in type 1 diabetic patients, sug
gesting an impairment of the entero-insular axis in both diabetic condition
s. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1
concentrations, both at fasting and in response to nutrient ingestion, in
16 type 1 diabetic patients (age = 40.5 +/- 14 yr, HbA1C = 7.8 +/- 1.5%), 1
4 type 2 diabetics (age = 56.5 +/- 13 yr, HbA1C = 8.1 +/- 1.8%), and 10 mat
ched controls. In postabsorptive state, a mixed breakfast (230 KCal) was ad
ministered to all subjects and blood samples were collected for plasma gluc
ose, insulin, C-peptide and GLP-1 determination during the following 3 hour
s. In normal subjects, the test meal induced a significant increase of GLP-
1 (30', 60': p < 0.01), returning the peptide values towards basal concentr
ations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to co
ntrols (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion fail
ed to increase plasma peptide levels, which even decreased during the test
(p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1
diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 p
g/ml). With respect to controls, the test meal induced in both diabetic gro
ups a significant increase in plasma glucagon levels at 60' (p < 0.01). In
conclusion, either in condition of insulin resistance or insulin deficiency
chronic hyperglycemia, which is a common feature of both metabolic disorde
rs, could induce a progressive desensitization of intestinal L-cells with c
onsequent peptide failure response to specific stimulation.