A novel long-acting glucose-dependent insulinotropic peptide analogue: enhanced efficacy in normal and diabetic rodents.
Bottom Line: AC163794 was synthesized by solid-phase peptide synthesis.AC163794 exhibited nanomolar functional GIP receptor potency in vitro similar to GIP and [d-Ala(2) ]GIP(1-42).AC163794 was metabolically more stable in vitro and displayed longer duration of insulinotropic action in vivo versus GIP and [d-Ala(2) ]GIP(1-42).
Affiliation: Amylin Pharmaceuticals, LLC, San Diego, CA, USA.Show MeSH
Related in: MedlinePlus
Mentions: In a glucose tolerance test performed at the end of the study in HF-STZ mice, fasting plasma glucose in AC163794-treated group was similar to concentrations in non-diabetic mice and significantly lower than in diabetic controls (p < 0.05) (Table 2). Glucose excursions had a trend to be reduced when compared with diabetic controls and AUC0-2h to be elevated relative to non-diabetic controls (figure 7A). FIns concentrations were significantly higher in AC163794-treated group than in diabetic counterparts (p < 0.05, Table 2). Glucose-stimulated insulin concentrations and AUC0–2h were not significantly different between AC163794- and vehicle-treated diabetic groups and significantly reduced versus non-diabetic controls (p < 0.05, figure 7B). Calculated values for HOMA-R and HOMA-B along with measured terminal percentage of body fat, hepatic lipid content, plasma adipokines (Il-6, Resistin, PAI-1), cholesterol and triglycerides are presented in Table 2. AC163794 improved insulin sensitivity and β-cell function, and had no effect on body fat content and fat metabolism-related endpoints.