Combination Therapy of an Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein and Peroxisome Proliferator-Activated Receptor γ Agonist in Diabetic Rat

Abstract EN

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.