Nateglinide Suppresses Postprandial Hypertriglyceridemia in Zucker Fatty Rats and Goto-Kakizaki Rats : Comparison with Voglibose and Glibenclamide
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概要
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Postprandial hypertriglyceridemia, as well as postprandial hyperglycemia, are important factors contributing to the development of cardiovascular disease in patients with type 2 diabetes. Nateglinide is a recently approved antidiabetic that suppresses postprandial hyperglycemia by stimulating the early phase of insulin secretion. In the present study, we investigated the effects of nateglinide on postprandial hypertriglyceridemia in obese Zucker fatty (ZF) rats and non-obese diabetic Goto-Kakizaki (GK) rats. Administration of an oral fat load caused marked hypertriglyceridemia with a peak at 2h in ZF and GK rats. Nateglinide (50 mg/kg) significantly suppressed the increase of plasma triglycerides after fat loading in both types of rat (△AUC [O-4 h]: 15±69mg・h/dl for nateglinide vs. 838±100 mg・h/dl for vehicle in ZF rats; p<O.O1, 81±22 mg・h/dl for nateglinide vs. 164±17mg・h/dl for vehicle in GK rats; p<O.O1). In contrast, other antidiabetic agents (voglibose and glibenclamide) did not show a significant effect on the increase of triglycerides after fat loading. The triglyceride components suppressed by nateglinide were mainly at the origin and in the pre β subfraction on agarose gel electrophoresis, suggesting that chylomicrons and very low density lipoproteins were decreased. Plasma insulin levels were significantly increased at 30 min in nateglinide-treated rats, but not in voglibose- or glibenclamide-treated rats. These results suggest that nateglinide not only suppresses postprandial hyperglycemia, but also suppresses postprandial hypertriglyceridemia, by promoting rapid and pulsatile insulin secretion in patients with type 2 diabetes.
- 公益社団法人日本薬学会の論文
- 2002-11-01
著者
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Kawamori R
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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Kawamori Ryuzo
聖マリアンナ医科大学 代謝･内分泌内科
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Kawamori Ryuzo
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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Okano A
National Institute Of Livestock And Grassland Science
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Okano A
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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Okano Akira
Pharmaceutical Research Laboratories Ajinomoto Co. Inc
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Kawamori Ryuzo
Department Of Medicine Juntendo University School Of Medicine
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KITAHARA YOSHIRO
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc.
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MIURA KYOKO
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc.
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Kanno Rei
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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Miura Kyoko
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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Mine Tomoyuki
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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MINE Tomoyuki
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc.
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Kitahara Y
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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Mita Tomoya
Department Of Medicine Metabolism And Endocrinology Juntendo University School Of Medicine
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Kitahara Yoshiro
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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