Hypoglycemic Agent YM440 Ameliorates the Impaired Hepatic Glycogenesis After Glucose Loading by Increasing Glycogen Synthase Activity in Obese Zucker Rats
| Autor: | Eiji Kurosaki, Akiyoshi Shimaya, Ryosuke Nakano, Masayuki Shibasaki, Hisataka Shikama, Kazuhiro Momose, Takayuki Suzuki |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Glucose loading medicine.medical_treatment chemistry.chemical_compound Internal medicine medicine Animals Hypoglycemic Agents Saline Pharmacology Glycogen synthase activity Oxadiazoles Glycogen Chemistry Glycogen metabolism Liver Glycogen Rats Rats Zucker Enzyme Activation Glycogen Synthase Endocrinology Liver Gluconeogenesis Glycogenesis Zucker Rats |
| Zdroj: | Japanese Journal of Pharmacology. 89:274-281 |
| ISSN: | 0021-5198 |
| Popis: | We studied the role of hepatic glycogenesis in glucose intolerance after glucose loading in obese Zucker rats and the effects of YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phen-oxy}but-2-ene) on it. Lean and obese Zucker rats were treated with YM440 (300 mg/kg) for 14 days and then fasted for 20 h. Thirty percent glucose (0.6 g/kg) or saline was administered intravenously followed by NaH 1 4 CO 3 . Gluconeogenesis was evaluated based on the incorporation of 1 4 C-bicarbonate into blood glucose and hepatic glycogen. Obese rats showed an increase in the incorporation of 1 4 C into blood glucose of 2,5-fold compared to lean rats. The glucose loading decreased the 1 4 C-blood glucose release by 18% in obese rats and 43% in lean rats at 45 min. Glucose loading increased the hepatic glycogen content and 1 4 C incorporation into glycogen in lean but not obese rats. YM440 decreased levels of fasting plasma insulin and blood glucose and the hepatic glycogen content by 50% compared with values for untreated obese rats. After glucose loading, YM440 promoted the incorporation of 1 4 C into glycogen and glycogen synthase activity, leading to an improvement in glucose tolerance. These results indicate that glucose intolerance in obese rats was associated with decreased hepatic glycogenesis and YM440 improved the intolerance by normalizing glycogen metabolism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|