产品描述:
Cotadutide is a synthetic peptide and dual agonist of the glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) that is biased toward GLP-1R.{66758,66759} It increases cAMP accumulation in CHO cells overexpressing recombinant human GLP-1R or GCGR (EC50s = 6.9 and 10.2 pM, respectively).{66758} It also enhances glucose-stimulated insulin secretion in INS-1 832/3 rat pancreatic β-cells. Cotadutide (10 nmol/kg) reduces food intake and fat mass, as well as improves glucose tolerance in diet-induced obese (DIO) mice. It also reduces food intake and body weight in wild-type but not Glp1r knockout mice, indicating these effects are Glp-1r-dependent, but reduces the hepatic lipid percentage in both wild-type and Glp1r knockout mice, indicating this as a Gcgr-dependent effect.{66759} Cotadutide (10 nmol/kg) reduces total hepatic triglycerides, diglycerides, cholesterol, and free fatty acids, as well as reduces hepatic inflammation and fibrosis, in an ob/ob mouse model of non-alcoholic steatohepatitis (NASH) induced by a high-trans fat, high-fructose, and high-cholesterol diet.