Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro

Changing ambient glucose concentration from 3 mmol/L to 10 mmol/L stimulated insulin secretion 9.8 +/- 1.3-fold.

• Exendin-4 and GLP-1 increased glucose-stimulated insulin secretion by up to 5.8 +/- 1.6-fold and 3.3 +/- 1.0-fold, respectively, over basal rates at 3 mmol/L glucose.
• At 10 mmol/L glucose, insulin secretion was increased by exendin-4 and GLP-1 up to 19.6 +/- 2.3-fold and 15.0 +/- 3.1-fold, respectively.
• In dynamically perfused isolated islets at 7.5 mmol/L glucose, insulin secretion increased 6.4 +/- 1.5-fold, with exendin-4 and GLP-1 enhancing this by up to 13.5 +/- 2.8 and 12.7 +/- 3.9-fold, respectively.
• In anesthetized rats, administration of 5.7 mmol/kg intravenous glucose led to a 3.0-fold increase in plasma insulin concentration.
• Infusion of exendin-4 or GLP-1 raised insulin concentration to a maximum of 7.6-fold and 5.3-fold, respectively, following glucose challenge.
• Both exendin-4 and GLP-1 demonstrated bell-shaped dose responses, with peak insulinotropic effects occurring at plasma peptide concentrations around 1 nmol/L.

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