A Novel Adrenaline Derivative, AZO02, and Its Hypoglycemic Action in Yellow KK Mice

抄録

AZO02 (L-threo-(3, 4-dihydroxy phenyl)-N-methyl serine methyl ester) is a newly synthesized adrenaline derivative. AZO02 caused relaxation of rat jejunum β₃-receptors) (ED₅₀=18μM), but did not affect the atrial rate (β₁) or tracheal relaxation (β₂) at a concentration of 0.3 mM. The pA₂ values for propranolol in inhibiting the isoproterenol- and AZOO2-stimulated relaxation of rat jejunum were 6.27 and 6.33, respectively. Thus, AZO02 is a selective agonist for β₃-adrenoceptor. AZO02 stimulated lipolysis (ED₅₀=10 μM) and glucose uptake (ED₅₀=1 μM) in rat adipocytes. In both cases, stimulation was antagonized by high concentrations of the β-adrenoceptor antagonist propranolol, but not by the α-adrenoceptor antagonist phentolamine. The effect of AZO02 on glucose uptake was synergistic with that of insulin. AZO02 was also assessed in vivo by using genetically obese mice (KK/Ay strain) with hyperglycemia. Administration of AZO02 in the diet for a week decreased blood glucose and non-esterified fatty acids.