ISSN:
1432-0428
Keywords:
Keywords Exendin-4
;
glucose
;
GLP-1
;
db/db mice
;
Wistar rats.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Glucagon-like peptide-1 is the main hormonal mediator of the enteroinsular axis. Recently, it has additionally received considerable attention as a possible new treatment for Type II (non-insulin-dependent) diabetes mellitus. Its major disadvantage is that its duration of action is too short to achieve good 24-h metabolic control. Exendin-4, which is produced in the salivary glands of Gila monster lizards, is structurally similar to glucagon-like peptide-1 and shares several useful biological properties with glucagon-like peptide-1. It binds the glucagon-like peptide-1 receptor, stimulates insulin release and increases the cAMP production in beta cells. We report that exendin-4 is a more potent insulinotropic agent when given intravenously to rats than is glucagon-like peptide-1 (ED50 0.19 nmol/kg for glucagon-like peptide-1 vs 0.0143 nmol/kg for exendin-4) and causes a greater elevation in cAMP concentrations in isolated islets. Of even greater interest we found that when given intraperitoneally only once daily to diabetic mice it had a prolonged effect of lowering blood glucose. After 1 week of treatment blood glucoses were 5.0 ± 2.6 mmol/l compared to diabetic concentrations of 13.2 ± 2.8 mmol/l. After 13 weeks of daily treatment HbA1 c was 8.8 ± 0.4 % in non-treated diabetic animals compared with 4.7 ± 0.25 % in treated diabetic animals. Blood glucoses also were lower (p 〈 0.005) and insulin concentrations higher (p 〈 0.02) in the treated animals. Exendin-4 could therefore be preferable to glucagon-like peptide-1 as a long-term treatment of Type II diabetes. [Diabetologia (1999) 42: 45–50]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250051111
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