Mechanism of action of hypoglycemic effects of an intestine-specific inhibitor of  microsomal triglyceride transfer protein (MTP) in XXXX @entity35 .

@entity13897 @entity28 @entity6 @entity71563 @entity1062 @entity35 @entity15212 @entity1720 @entity1602
Diminished insulin sensitivity in the peripheral tissues and failure of pancreatic beta cells to secrete insulin are known major determinants of @entity6 . @entity71563 , an intestine-specific microsomal transfer protein inhibitor, has been shown to suppress high fat-induced @entity28 and ameliorate @entity13897 while enhancing @entity15212 ( @entity15212 ) secretion. We investigated the effects of @entity71563 on glucose metabolism and elucidated the mechanism of action, direct effects on insulin sensitivity and glucose-stimulated insulin secretion in a high fat diet-induced @entity28 @entity35 model. Male @entity35 fed a high-fat diet were treated with a single administration of @entity71563 . Glucose tolerance, @entity1602 clamp and hyperinsulinemic-euglycemic testing were performed to assess effects on insulin sensitivity and glucose-stimulated insulin secretion, respectively. Plasma @entity15212 and tissue triglyceride content were also determined under the same conditions. A single administration of @entity71563 suppressed plasma glucose elevations after oral glucose loading and increased the disposition index while elevating @entity15212 . @entity71563 also enhanced glucose-stimulated insulin secretion in @entity1602 clamp tests, whereas @entity1720 was observed in @entity1062 . Single-dose administration of @entity71563 decreased lipid content in the liver and skeletal muscle. @entity71563 demonstrated acute and direct hypoglycemic effects by enhancing insulin secretion and/or insulin sensitivity.
