Insulinlike Activity of New Antidiabetic Agent CP 68722 in 3T3-L1 Adipocytes
| Autor: | R W Stevenson, David K. Kreutter, K. M. Andrews, E. M. Gibbs, N. J. Hutson |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Glucose uptake medicine.medical_treatment Stimulation Deoxyglucose Cycloheximide Cell Line chemistry.chemical_compound Insulin resistance Internal medicine Adipocyte Internal Medicine medicine Animals Insulin Benzopyrans Cells Cultured Dose-Response Relationship Drug Chemistry Temperature Glucose transporter Biological Transport 3T3-L1 medicine.disease Receptor Insulin Thiazoles Glucose Sulfonylurea Compounds Endocrinology Adipose Tissue Diabetes Mellitus Type 2 Thiazolidinediones Insulin Resistance Oxidation-Reduction |
| Zdroj: | Diabetes. 39:1414-1419 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | We examined the in vitro effects of CP 68722, a novel antidiabetic agent, in 3T3-L1 adipocytes. CP 68722 stimulated 2-deoxyglucose uptake in the absence of insulin. At least 30 min of incubation were required for stimulation of uptake. This effect increased over 5 h and was sustained up to 72 h. The stimulation of 2-deoxyglucose uptake by CP 68722 could be inhibited ∼60% by inhibition of protein synthesis with cycloheximide. Half-maximal and maximal responses to CP 68722 at 72 h of incubation were observed at 10 and 100 μM of drug, respectively, with a threefold stimulation of uptake at 100 μM approximating the maximal response of these cells to acute insulin stimulation. CP 68722 was able to overcome insulin resistance induced by dexamethasone in 3T3-L1 cells. The effect of drug, like that of insulin, was primarily to increase the Vmax of 2-deoxyglucose uptake. The stimulation of uptake by CP 68722 or insulin could be prevented by incubating the cells at 10°C, a temperature that impedes translocation of glucose transporters to the plasma membrane. Therefore, it appears that CP 68722, like insulin, stimulates glucose uptake by a mechanism that involves translocation of intracellular glucose transporters to the plasma membrane and de novo protein synthesis. We compared the effect of CP 68722 with the sulfonylureas, the primary drugs used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). CP 68722 was a more potent and effective stimulator of 2-deoxyglucose uptake in 3T3-L1 cells than either first- or second-generation sulfonylureas. Our results suggest that CP 68722 could be an effective therapeutic agent for the treatment of NIDDM. |
| Databáze: | OpenAIRE |
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