Combination therapy of an intestine-specific inhibitor of microsomal triglyceride transfer protein and peroxisome proliferator-activated receptor γ agonist in diabetic rat

We investigated effects on glucose and lipid metabolism in combination of jtt-130,a novel intestine-specific microsomal triglyceride transfer protein (mtp) inhibitor,and pioglitazone,peroxisome proliferator-activated receptor (ppar) γ agonist. male zucker diabetic fatty rats were divided into 4 groups: control group,jtt-130 treatment group,pioglitazone treatment group,and combination group. the zucker diabetic fatty rats were fed a regular powdered diet with jtt-130 and/or pioglitazone as a food admixture for 6 weeks. effects on glucose and lipid metabolism were compared mainly between jtt-130 treatment group and combination group. jtt-130 treatment showed good glycemic control,while the plasma glucose and glycated hemoglobin levels in combination group were significantly decreased as compared with those jtt-130 treatment group. the reduction in the plasma triglyceride and free fatty acid levels in combination group was higher than that in jtt-130 treatment group,and glucose utilization was significantly elevated in adipose tissues. in zucker diabetic fatty rats,combination treatment of jtt-130 and pioglitazone showed better glycemic control and a strong hypolipidemic action with an enhancement of insulin sensitivity. combination therapy of mtp inhibitor and pparγ agonist might be more useful in the treatment of type 2 diabetes accompanied with obesity and insulin resistance. © 2014 shohei sakata et al.