cAMP-GEFII ·Rim2 pat hway is involved in the K+-channel-independent mechanism of insulinnotropic act ivity of new imidazoline compound BL 11282
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-GEFIIRim2 pathway in BL11282-stimulated insulin secretion.