ANTIOBESITY AND ANTIDIABETIC EFFECTS OF CARTEOLOL IN NON-INSULIN-DEPENDENT DIABETIC MICE

1. When carteolol, a beta-adrenergic blocker, was administered to KK-A (Y)/Ta Jc1 mice that are obese and develop spontaneously non-insulin d ependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenc ed by carteolol treatment, compared with the control KK-A(Y)/Ta Jc1 mi ce, abolition of the weight gain might be attributed to increased ener gy metabolism. 2. Non-fasting serum glucose levels in carteolol-treate d mice at the age of 17 weeks were within normal range(118+/-4 vs 186/-12 mg/dL). An intraperitoneal glucose-tolerance test revealed that t he carteolol treatment markedly restored glucose metabolism; fasting p lasma glucose (88+/-6 mg/dL) was within normal range, and immunoreacti ve insulin (IRI; 5.8+/-0.8 vs 33.3+/-10.5 ng/mL) and plasma glucose le vels at 60 min post glucose (361+/-44 vs 541+/-32 mg/dL) were signific antly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considere d to have little effect on the growth of mice but to correct the obesi ty that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IR I levels suggests that carteolol improves glucose tolerance by increas ing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is cl osely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT. When the regional blood flow was mea sured by radioactive microspheres in rats, blood flow in BAT and white adipose tissue was markedly increased by carteolol. 5. These findings indicate that carteolol blocks beta(1)- and beta(2)-adrenoceptors, bu t may stimulate beta(3)-receptors particularly in the adipose tissue t o promote lipolysis and thermogenesis, and to consume excess energy in mice. Thus, carteolol does not influence mouse growth, but may preven t obesity leading to increases in insulin sensitivity.