Nateglinide suppresses postprandial hypertriglyceridemia in Zucker fatty rats and Goto-Kakizaki rats: comparison with voglibose and glibenclamide.
Biol Pharm Bull
; 25(11): 1412-6, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12419950
ABSTRACT
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 2 h in ZF and GK rats. Nateglinide (50 mg/kg) significantly suppressed the increase of plasma triglycerides after fat loading in both types of rat (delta AUC [0-4 h] 15+/-69 mg.h/dl for nateglinide vs. 838+/-100 mg.h/dl for vehicle in ZF rats; p<0.01, 81+/-22 mg x h/dl for nateglinide vs. 164+/-17 mg.h/dl for vehicle in GK rats; p<0.01). 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 beta 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.
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Base de dados:
MEDLINE
Assunto principal:
Fenilalanina
/
Hipertrigliceridemia
/
Glibureto
/
Período Pós-Prandial
/
Cicloexanos
/
Inositol
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article