Clofibrate has long been used as a hypolipidemic drug. Recently, it has been shown to improve glucose tolerance without increasing serum insulin levels during challenge tests in diabetics. We have studied the effect of 2-(p-chlorophenoxyisobutyrate)(CPIB)(the active form of clofibrate) on insulin actions and insulin receptors in isolated rat adipocytes.
CPIB stimulated conversion of [2-³H]-glucose to total lipids (lipogenesis) dose-dependently within therapeutic dose limits (0-200μg/ml). CPIB (200μg/ml) stimulated lipogenesis approximately 2-fold and enhanced the insulin responsiveness of lipogenesis about 2-fold compared with nontreated adipocytes. CPIB also stimulated [³H]-2-deoxyglucose transport to adipocytes and enhanced this effect of insulin at lower insulin concentrations.
However, there was no significant difference between CPIB-treated and non-treated adipocytes in ¹²⁵I-insulin binding capacity. When cultured human lymphocytes (IM-9) were exposed to 200μg/ml CPIB over 24 hr, there was also no significant difference in ¹²⁵I-insulin binding capacity between control and treated cells.
These results demonstrate that CPIB has insulin-like effects on rat adipocytes, which can not be attributed to change in the affinity of insulin receptor sites, and suggest that CPIB acceleratets the post-receptor mechanism.