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1. The effects of KAD-1229 (a novel non-sulphonylurea agent), voglibose (an alpha-glucosidase inhibitor) and nateglinide (a non-sulphonylurea antihyperglycaemic agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats. 2. KAD-1229 suppressed the increase in plasma glucose levels seen after a meal load and the area under the curve for plasma glucose levels (AUCglucose) up to 5 h after the meal load. 3. Voglibose also suppressed the increase in plasma glucose levels; however, a significant decrease in AUCglucose following voglibose was not observed. 4. Nateglinide suppressed the increase in plasma glucose levels at 30 min and 1 h after the meal load; however, plasma glucose levels was above control thereafter and the AUCglucose was not decreased. 5. The results indicate that KAD-1229 has an antihyperglycaemic effect and KAD-1229 is suggested to be a suitable agent for controlling post-prandial hyperglycaemia.

We investigated the effects of free radical generation on the esterification of cholesterol by lecithin-chelesterol acyltransferase (LCAT). A water-soluble free radical initia･ tor,2,2'-azobis-amidinopropanedihydrochloride(AAPH), inhibited the activity of plasma LCAT as a function of the incubatio" time after its addition. When a small amoullt of oxidized HDL was added to plasma, LCAT actiyity was dose-dependently inhibited. To identify the effects of HDL oxidation on LCAT actiyity, a purified enzyme and cofacter in a vesicle solution (an artificial substrate) were used. i) LCAT actiyity was inhibited by the oxidatien of substrate yesicles, this inhibition being Telated to the degree of oxidation. ii) This i"hibition was obseryed eyen if apolipoprotein A-I was not oxidized. lii) Oxidized phosphatidylcho]ine, but not exidized cholesterol, in the vesicles affected LCAT activity. iy) The addition of O-40% of oxidized vesicles to normal substrateyesicles resulted in the activity of LCAT being inhibited in a dose-dependent manner. These results suggest that the esterification of chelesterol by LCAT mfty be affected by the exidation of substrate phosphatidylcholine via free radical generation in the plasma.

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We tried to confirm the antioxidative capability of lecithin:cholesterol acyltransferase (LCAT) reported by Vohl et al. [Biochemistry (1999) 38, 5976-5981]. The enzyme solution protected LDL against oxidation. However, this protection was not due to LCAT enzyme, but to some unknown low-molecular-weight substance(s) in the solution; LCAT itself exerted little protective effect against LDL oxidation.