Imidazoline compound BL11282 possesses a pure glucose-dependent effect on insulin release and, therefore
can be considered as a promising antihyperglycemic agent for type 2 diabetes. The data obtained show that: 1) overnight
pretreatment of pancreatic islets with BL11282 desensitizes subsequent islet response to this imidazoline; 2) overnight
pretreatment with BL11282 is accompanied by an increased islet response to subsequent high glucose concentration; 3)
desensitization of islet response to BL11282 does not eliminate subsequent islet response to glucagon-like peptide-1 (GLP-1),
however, significantly decreases the fold stimulation of insulin release by this peptide. The latter effect points out to the
importance of GLP-1 in insulinotropic activity of BL11282. Our results support the involvement of cAMP-GEFII·Rim2
pathway in BL11282-stimulated insulin secretion.