Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent
| Autor: | Takeshi Fujita, Takashi Sohda, Yasuo Sugiyama, Shigehisa Taketomi, Ziro Suzuoki, Yutaka Kawamatsu, Hisashi Iwatsuka |
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| Rok vydání: | 1983 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.medical_treatment Endocrinology Diabetes and Metabolism Mice Obese Fatty Acids Nonesterified Diabetes Mellitus Experimental chemistry.chemical_compound Mice Insulin resistance Dogs Internal medicine Diabetes mellitus Hyperinsulinemia Diabetes Mellitus Internal Medicine Medicine Glucose test Animals Hypoglycemic Agents Insulin Obesity Phospholipids Triglycerides medicine.diagnostic_test Triglyceride business.industry Insulin tolerance test Hypertriglyceridemia Rats Inbred Strains medicine.disease Rats Thiazoles Endocrinology Cholesterol chemistry Thiazolidinediones Insulin Resistance business |
| Zdroj: | Diabetes. 32:804-810 |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/diabetes.32.9.804 |
| Popis: | Effects of 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, Ciglitazone) on glucose and lipid metabolism were examined in various animal models. ADD-3878, administered as a dietary admixture (30–186 mg/kg/day) to obese-diabetic yellow KK (KK-Ay) mice, markedly suppressed the diabetic syndromes (hyperglycemie, hypertriglyceride-mia, and hyperinsulinemia), accompanied by the reduction of insulin resistance as manifested by improvement of overall insulin sensitivity in either the insulin tolerance test òr the steady-state blood glucose test. Chronic administration of ADD-3878 for as long as 12 wk to young yellow KK mice, which were in the early stage of diabetes and obesity, depressed age-dependent rises in blood glucose, plasma triglyceride, and insulin without exerting any effect on obesity. When orally administered to obese Zucker-fatty rats, ADD-3878 decreased plasma insulin and triglyceride in a dose-dependent manner (5–100 mg/kg/day). The treated rats showed increased tolerance and decreased insulin secretion in response to oral glucose. The glycemie response to insulin and the steady-state plasma glucose were also normalized in the treated rats. Chronic administration of ADD-3878 to young fatty rats for as long as 12 wk decreased the dose-dependent rises in blood glucose, plasma triglyceride, and insulin without exerting any effect on body weight. ADD-3878 had no effect on glucose and lipid metabolism of young Sprague-Dawley rats and mild strepto-zotocin-diabetic rats. However, in old Sprague-Dawley rats that were moderately insulin resistant and hyperli-pidemic compared with young ones, ADD-3878 decreased plasma triglyceride and insulin and improved insulin sensitivity. Five-day administration of ADD-3878 to beagle dogs with slightly impaired glucose tolerance increased glucose tolerance and suppressed postprandial rises in plasma glucose, insulin, and triglyceride. Based on these results, ADD-3878 is effective on abnormal glucose and lipid metabolism associated with insulin resistance or obesity through reduction of peripheral insulin resistance. Therefore, ADD-3878 is expected to be useful in the treatment of hyperglycemie, hyperinsulinemia, and hyperlipemia in obese type II diabetes and Obesity. |
| Databáze: | OpenAIRE |
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