Ciglitazone, a New Hypoglycemic Agent: II. Effect on Glucose and Lipid Metabolisms and Insulin Binding in the Adipose Tissue of C57BL/6J-ob/ob and − + / ? Mice

The fat pads isolated from control and ciglitazone-treated C57BL/6J-ob/ob mice and their lean littermates (− + / ?) were incubated in vitro with glucose-1-¹⁴C/-5-³H in the presence of insulin. The formation of ¹⁴CO₂ and ³H₂O and the levels of free fatty acids and glycerol in the medium and the incorporation of ¹⁴C and ³H into esterified lipids and free fatty acids in the fat pads were measured. The basal rates of glucose-1-¹⁴C/-5-³H metabolism per unit weight were increased in the fat pads of ciglitazone-treated mice, more pronouncedly in the treated lean than in the treated obese. The insulin-dependent effects were enhanced in the treated ob/ob mice. To see the dose-response of insulin, a second experiment was carried out in which portions of the fat pads were incubated in vitro with glucose-1-¹⁴C in the presence of 0–40 ng/ml insulin and isolated adipo-cytes were used to estimate for ¹²⁵l-insulin binding. The basal rates of ¹⁴CO₂ and ¹⁴C-lipids formation per unit weight of fat pads were increased in both treated obese and treated lean groups but insulin-dependent elevation was seen only in the treated obese group. Ciglitazone significantly increased insulin binding capacity at the low-affinity sites in the adipocytes of obese mice but not in those of lean mice. The data showed that ciglitazone increased the basal rate of glucose metabolism, lipogenesis, insulin receptor numbers, and post-receptor responses in the C57BL/ 6J-ob/ob mice; it increased the basal rate of glucose metabolism and lipogenesis but not insulin sensitivity in the lean mice.