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Horm Metab Res 2002; 34(3): 150-154
DOI: 10.1055/s-2002-23199
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Evidence for Early Impairment of Glucagon-Like Peptide 1-Induced Insulin Secretion in Human Type 2 (Non Insulin-Dependent) Diabetes

R.  Lugari 1 , A.  Dei Cas 1 , D.  Ugolotti 1 , L.  Finardi 1 , A.  L.  Barilli 1 , C.  Ognibene 2 , A.  Luciani 2 , R.  Zandomeneghi 2 , A.  Gnudi 1
  • 1Department of Endocrinology, University of Parma, Parma, Italy
  • 2Department of Internal Medicine, University of Modena, Modena, Italy
These results were accepted for the 37th Annual Meeting of the European Society for the Study of Diabetes (E.A.S.D.), 9 - 13 September 2001, Glasgow, U.K.
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Publication History

3 July 2001

30 October 2001

Publication Date:
26 March 2002 (online)

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Abstract

To investigate a possible role of an enteroinsular axis involvement in the pathogenesis of type 2 diabetes, plasma glucagon-like peptide 1 (GLP-1) 7-36 amide response to nutrient ingestion was evaluated in type 2 diabetics affected by different degrees of β-cell dysfunction.

Methods: 14 patients on oral hypoglycaemic treatment (group A: HbA1C = 8.1 ± 1.8 %) and 11 age-matched diabetic patients on diet only (group B: HbA1C = 6.4 ± 0.9) participated in the study. 10 healthy volunteers were studied as controls. In the postabsorptive state, a mixed meal (700 kCal) was administered to all subjects, and blood samples were regularly collected up to 180′ for plasma glucose, insulin, glucagon, and GLP-1 determination.

Results: In the control group, the test meal induced a significant increase in plasma GLP-1 at 30′ and 60′ (p < 0.01); the peptide concentrations then returning toward basal levels. β-cell function estimation by HOMA score confirmed a more advanced involvement in group A than in group B (p < 0.01). In contrast, the insulin resistance degree showed a similar result in the two groups (HOMA-R). In group A, first-phase postprandial insulin secretion (0 - 60’) resulted, as expected, in being significantly reduced compared to healthy subjects (p < 0.001). In the same patients the mean fasting GLP-1 value was similar to controls, but the meal failed to increase plasma peptide levels, which even tended to decrease during the test (p < 0.01). In group B, food-mediated early insulin secretion was higher than in group A (p < 0.001), although significantly reduced when compared to controls (p < 0.01). Like group A, no GLP-1 response to food ingestion occurred in group B patients in spite of maintained basal peptide secretion. Whereas the test-meal did not significantly modify plasma glucagon levels in the control group, glucagon concentrations increased at 30’ and 60’ in both diabetic groups (p < 0.01).

Conclusions: 1) The functional integrity of GLP-1 cells results as being seriously impaired even in the condition of mild diabetes; 2) the early peptide failure could contribute to the development of β-cell deterioration which characterizes overt type 2 diabetes.

Key words

GLP-1 - Enteroinsular Axis - Diabetes

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