EFFECTS OF TROGLITAZONE AND METFORMIN ON GLUCOSE AND LIPID-METABOLISM- ALTERATIONS OF 2 DISTINCT MOLECULAR PATHWAYS

Troglitazone and metformin are antidiabetic agents that belong to the thiazolidinedione and biguanide classes of drugs, respectively. To eva luate how these drugs influence fuel utilization, we compared their ef fects on several pathways regulating carbohydrate and lipid metabolism in vitro. Both drugs stimulated glucose transport and utilization in C3H10T1/2 cells, a cell line capable of differentiating into adipocyte s when treated with thiazolidinediones. However, we observed that thes e drugs had a number of different in vitro effects. Unlike metformin, troglitazone stimulated beta(3)-adrenergic receptor-mediated lipolysis , lipogenesis, and transcriptional activity of the nuclear receptor pe roxisome proliferator-activated receptor gamma (PPAR gamma). Further, by using a mitochondrial-specific fluorescent dye, we found troglitazo ne to be more effective than metformin at increasing mitochondrial mas s. In contrast to troglitazone, metformin was more effective at increa sing mitochondrial fatty acid beta-oxidation, peroxisomal fatty acid b eta-oxidation, and anaerobic respiration (i.e. lactate production). Ad ditionally, metformin stimulated and troglitazone inhibited both aerob ic respiration and basal lipolysis. Insulin enhanced the effects of tr oglitazone, but not those of metformin, on these cells. Taken together , the data show that troglitazone and metformin affect two distinct me tabolic pathways: one that is anabolic (i.e. troglitazone) and the oth er that is catabolic (i.e. metformin). Further, these observations sug gest that the metabolic activity of mitochondria may be lower in cells treated with troglitazone than with metformin. (C) 1997 Elsevier Scie nce Inc.