Abstract: The present application relates to the secondary binding site of dipeptidyl peptidase IV, its relationship amongst substrates and to the modulation of substrate specificity of dipeptidyl peptidase IV (DP IV, synonym: DPP IV, CD26, EC 3.4.14.5). The application relates further to compounds that bind to the secondary binding site of DP IV and their use to modulate the substrate specificity of DP IV; methods of treatment of various DP IV mediated disorders; and screening methods for the identification of secondary binding sites on DP IV and DP IV-like enzymes.

Abstract: The present invention discloses methods for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic ?-cells, to cause differentiation of pancreatic epithelial cells into insulin producing ?-cells, to improve muscle sensitivity to insulin and other weight control efforts by the chronic oral administration of a DP IV-inhibitor. The administration causes the active form of GLP-1 and other non-nutrient stimulated growth hormones to remain biologically active longer under physiological conditions. The extended presence of such hormones, in particular in the pancreatic tissue can also facilitate differentiation and regeneration of the ?-cells already present that are in need of repair.

Abstract: The present invention discloses methods for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic ?-cells, to cause differentiation of pancreatic epithelial cells into insulin producing ?-cells, to improve muscle sensitivity to insulin and other weight control efforts by the chronic oral administration of a DP IV-inhibitor. The administration causes the active form of GLP-1 and other non-nutrient stimulated growth hormones to remain biologically active longer under physiological conditions. The extended presence of such hormones, in particular in the pancreatic tissue can also facilitate differentiation and regeneration of the ?-cells already present that are in need of repair.

Abstract: The present application relates to the secondary binding site of dipeptidyl peptidase IV, its relationship amongst substrates and to the modulation of substrate specificity of dipeptidyl peptidase IV (DP IV, synonym: DPP IV, CD26, EC 3.4.14.5). The application relates further to compounds that bind to the secondary binding site of DP IV and their use to modulate the substrate specificity of DP IV; methods of treatment of various DP IV mediated disorders; and screening methods for the identification of secondary binding sites on DP IV and DP IV-like enzymes.

Abstract: The present invention discloses methods for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic &bgr;-cells, to cause differentiation of pancreatic epithelial cells into insulin producing &bgr;-cells, to improve muscle sensitivity to insulin and other weight control efforts by the chronic oral administration of a DP IV-inhibitor. The administration causes the active form of GLP-1 and other non-nutrient stimulated growth hormones to remain biologically active longer under physiological conditions. The extended presence of such hormones, in particular in the pancreatic tissue can also facilitate differentiation and regeneration of the &bgr;-cells already present that are in need of repair.