التفاصيل البيبلوغرافية
| العنوان: |
Synergistic metabolic benefits of an exenatide analogue and cholecystokinin in diet-induced obese and leptin-deficient rodents. |
| المؤلفون: |
Trevaskis, J. L., Sun, C., Athanacio, J., D'Souza, L., Samant, M., Tatarkiewicz, K., Griffin, P. S., Wittmer, C., Wang, Y., Teng, C.‐H., Forood, B., Parkes, D. G., Roth, J. D. |
| المصدر: |
Diabetes, Obesity & Metabolism; Jan2015, Vol. 17 Issue 1, p61-73, 13p |
| مصطلحات موضوعية: |
CHOLECYSTOKININ, LEPTIN, GLUCAGON-like peptide 1, EXPERIMENTAL pharmacology, WEIGHT loss, HYPOGLYCEMIC agents |
| مستخلص: |
Aim To test the impact of cholecystokinin ( CCK) plus either amylin or a glucagon-like peptide-1 receptor ( GLP-1R) agonist on metabolic variables in diet-induced obese ( DIO) rodents. Methods A stabilized acetylated version of CCK-8 (Ac-Y*- CCK-8), selective CCK1 receptor ( CCK1R) or CCK2 receptor ( CCK2R) agonists, amylin or the GLP-1R agonist and exenatide analogue AC3174 were administered in select combinations via continuous subcutaneous infusion to DIO rats for 14 days, or Lepob/Lepob mice for 28 days, and metabolic variables were assessed. Results Combined administration of Ac-Y*- CCK-8 with either amylin or AC3174 induced greater than additive weight loss in DIO rats, with the overall magnitude of effect being greater with AC3174 + Ac-Y*- CCK-8 treatment. Co-infusion of AC3174 with a specific CCK1R agonist, but not a CCK2R agonist, recapitulated the weight loss mediated by AC3174 + Ac-Y*- CCK-8 in DIO rats, suggesting that synergy is mediated by CCK1R activation. In a 4 × 4 full-factorial response surface methodology study in DIO rats, a synergistic interaction between AC3174 and the CCK1R-selective agonist on body weight and food intake was noted. Co-administration of AC3174 and the CCK1R-selective agonist to obese diabetic Lepob/Lepob mice elicited a significantly greater reduction in percentage of glycated haemoglobin and food intake relative to the sum effects of monotherapy groups. Conclusions The anti-obesity and antidiabetic potential of combined GLP-1R and CCK1R agonism is an approach that warrants further investigation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |