ISSN:
1432-5233
Keywords:
Key words Glucagon-like-peptide-1
;
Prediabetes
;
NOD mouse
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The effect of the insulinotropic gut hormone glucagon-like-peptide-1 (GLP-1) was studied on the residual insulin capacity of prediabetic nonobese diabetic (NOD) mice, a model of insulin-dependent diabetes mellitus (type 1). This was done using isolated pancreas perfusion and dynamic islet perifusion. Prediabetes was defined by insulitis and fasting normoglycemia. Insulitis occurred in 100% of NOD mice beyond the age of 12 weeks. K values in the intravenous glucose tolerance test were reduced in 20-week-old NOD mice compared with age-matched non-diabetes-prone NOR (nonobese resistant) mice (2.4±1.1 vs 3.8±1.5% min–1, P〈0.05). Prediabetic NOD pancreases were characterized by a complete loss of the glucose-induced first-phase insulin release. In perifused NOD islets GLP-1, at concentrations already effective in normal islets, left the insulin release unaltered. However, a significant rise of glucose-dependent insulin secretion occurred for GLP-1 concentrations 〉0.1 nM. This was obtained with both techniques, dynamic islet perifusion and isolated pancreas perfusion, indicating a direct effect of GLP-1 on the beta-cell. Analysis of glucose-insulin dose-response curves revealed a marked improvement of glucose sensitivity of the NOD endocrine pancreas in the presence of GLP-1 (half-maximal insulin output without GLP-1 15.2 mM and with GLP-1 9.4 mM, P〈0.002). We conclude that GLP-1 can successfully reverse the glucose sensing defect of islets affected by insulitis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00571935
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