Positive effects of GLP-1 receptor activation with liraglutide on pancreatic islet morphology and metabolic control in C57BL/KsJ db/db mice with degenerative diabetes.

Stable glucagon-like peptide-1 (GLP-1) mimetics, such as the GLP-1 analogue liraglutide, are approved for treatment of type 2 diabetes. GLP-1 has a spectrum of anti-diabetic effects that are of possible utility in the treatment of more severe forms of diabetes. The present study has evaluated the effect of once daily liraglutide injection (25 nmol/kg bw) for 15 days on metabolic control, islet architecture, and islet morphology in C57BL/KsJ db/db mice. Liraglutide had no appreciable effects on body weight, food intake, and non-fasting glucose and insulin concentrations. However, HbA1c was significantly (p¿<¿0.001) decreased, and oral glucose tolerance improved in liraglutide treated db/db mice. Pancreatic insulin content was increased (p¿<¿0.05) compared with saline controls, and the ratio of pancreatic insulin to glucagon in liraglutide mice was similar to lean mice. Although liraglutide did not alter islet number or area, the proportion of beta cells per islet was significantly increased (p¿<¿0.05) and alpha cells decreased (p¿<¿0.05), with normalization of islet architecture.