Combined effects of troglitazone and muscle contraction on insulin sensitization in Balb-c mouse muscle

Thiazolidinediones, represented by troglitazone, are insulin-sensitizing ag ents with proven efficacy for the treatment of type 2 diabetes. Exercise is also recommended for patients with type 2 diabetes because it both stimula tes glucose uptake directly and it increases insulin sensitivity following exercise. The purpose of this study was to investigate the effects of trogl itazone combined with exercise on 2-deoxyglucose (2DG) uptake in both the e pitrochlearis and soleus muscle of Balb-c mice. Acute, 1-h treatment with t roglitazone (10 or 20 muM), in the presence or absence of insulin, had no e ffect on 2DG uptake in either muscle. Chronic treatment with troglitazone b y feeding enhanced the insulin sensitivity and responsiveness of 2DG uptake primarily in the epitrochlearis. Direct electrical stimulation of in situ muscle was used to model exercise while the contralateral muscle was used a s the unexercised control. This model mimicked exercise in that glycogen wa s depleted, immediate 2DG uptake was enhanced, and there was a post-exercis e increase in insulin sensitivity. Troglitazone feeding had no effect on 2D G uptake in the soleus when measured immediately after electrical stimulati on. However, 2DG uptake in the unstimulated epitrochlearis from troglitazon e-fed mice was elevated when measured immediately after removal such that n o additional effects of the electrical stimulation were measured. We found that the insulin-sensitizing effect of troglitazone was not additive to the insulin-sensitizing effect of exercise, which suggests that troglitazone a nd exercise share similar pathways. A unique finding in this study was the differential response to troglitazone between the epitrochlearis (fast twit ch) and the soleus (slow twitch) muscle types. Possible mechanisms are disc ussed. (C) 2001 societe francaise de biochimie et biologic moleculaire/Edit ions scientifiques et medicales Elsevier SAS. All rights reserved.