Glucagon-like peptide-1 and the entero-insular axis in obese hyperglycaemic (ob/ob)mice

Abstract

The intestines of obese hyperglycaemic (ob/ob) mice contain greatly increased amounts of glucagon-like immunoreactive peptides. To investigate their role in the increased activity of the entero-insular axis of these mice, the insulin-releasing effect of glucagon-like peptide-1 (GLP-1) was examined in 24 hour fasted 12–15 weeks old ob/ob mice under conditions of basal and elevated glycaemia. Compared with glucagon (100 ug/kg ip), which produced an approximately 3-fold increase in basal plasma glucose and insulin concentrations, GLP-1 (100 ug/kg ip) produced a very small (less than 1 fold) increase in plasma insulin, with no significant change in plasma glucose. The insulin-releasing effect of glucagon, but not GLP-1 was increased by administration in combination with glucose (2 g/kg ip). The results indicate that GLP-1, which exhibits considerable sequence homology with glucagon, exerts only a weak insulin-releasing effect without a significant hyperglycaemic effect in ob/ob mice. Thus GLP-1 is unlikely to be an important endocrine component of the over-active entero-insular axis in ob/ob mice.