JTT-130,a Novel Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein,Improves Hyperglycemia and Dyslipidemia Independent of Suppression of Food Intake in Diabetic Rats

We investigated the effects of jtt-130 on glucose and lipid metabolism independent of the suppression of feeding by comparing with pair-fed animals. male zucker diabetic fatty (zdf) rats were divided into control,jtt-130 treatment,and pair-fed groups. the rats were fed with a regular powdered diet with or without jtt-130 as a food admixture for 6 weeks. we compared the effects on glucose and lipid metabolism in jtt-130 treatment group with those in pair-fed group. results. hyperglycemia in zdf rats was prevented in both jtt-130 treatment and pair-fed groups,but the prevention in pair-fed group became poor with time. moreover,reduction in plasma cholesterol levels was observed only in jtt-130 treatment group. jtt-130 treatment group showed improved glucose tolerance at 5 weeks after treatment and significant elevation of portal glucagon-like peptide-1 (glp-1) levels. the hepatic lipid content in jtt-130 treatment group was decreased as compared with pair-fed group. furthermore,pancreatic protection effects,such as an increase in pancreatic weight and an elevation of insulin-positive area in islets,were observed after jtt-130 treatment. conclusions. jtt-130 improves hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake,which is ascribed to an enhancement of glp-1 secretion and a reduction of lipotoxicity. © 2014 shohei sakata et al.