scholarly journals Combination Therapy of an Intestine-Specific Inhibitor of Microsomal Triglyceride Transfer Protein and Peroxisome Proliferator-Activated ReceptorγAgonist in Diabetic Rat

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shohei Sakata ◽  
Yasuko Mera ◽  
Yukiharu Kuroki ◽  
Reiko Nashida ◽  
Makoto Kakutani ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Treatment Group ◽  
Glycemic Control ◽  
Combination Therapy ◽  
Microsomal Triglyceride Transfer Protein ◽  
Combination Group ◽  
Peroxisome Proliferator ◽  
Transfer Protein ◽  
Glucose And Lipid Metabolism ◽  
Zucker Diabetic Fatty Rats

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)γagonist. 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 PPARγagonist might be more useful in the treatment of type 2 diabetes accompanied with obesity and insulin resistance.

scholarly journals 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

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shohei Sakata ◽  
Makoto Ito ◽  
Yasuko Mera ◽  
Tomohiko Sasase ◽  
Hiromi Yamamoto ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Treatment Group ◽  
Food Intake ◽  
Plasma Cholesterol ◽  
Specific Inhibitor ◽  
Microsomal Triglyceride Transfer Protein ◽  
Diabetic Rats ◽  
Glucose And Lipid Metabolism ◽  
Zdf Rats ◽  
Glucagon Like Peptide 1

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.

scholarly journals The Roots ofAtractylodes macrocephalaKoidzumi Enhanced Glucose and Lipid Metabolism in C2C12 Myotubes via Mitochondrial Regulation

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mi Young Song ◽  
Seok Yong Kang ◽  
Tae Woo Oh ◽  
Rethineswaran Vinoth Kumar ◽  
Hyo Won Jung ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Mitochondrial Function ◽  
Weight Control ◽  
Glucose Consumption ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Glucose And Lipid Metabolism

The root ofAtractylodes macrocephalaKoidzumi (Atractylodis Rhizoma Alba, ARA) is a Traditional Korean Medicine and has been commonly used for weight control. Mitochondrial dysfunction appears to be a key contributor to insulin resistance, and therefore mitochondrial targeting drugs represent an important potential strategy for the treatment of insulin resistance and obesity. In this study, the authors investigated the regulatory effects of ARA on mitochondrial function with respect to the stimulation of glucose and lipid metabolism in C2C12 myotubes. After differentiating C2C12 myotubes, cells were treated with or without different concentrations (0.2, 0.5, and 1.0 mg/mL) of ARA extract. ARA extract significantly increased the expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC1α) and the downregulations of its targets, nuclear respiratory factor-1 (NRF-1), transcription factor A (TFAM), and total ATP content in C2C12 myotubes. ARA extract also increased the expressions of PGC1αactivator and of the metabolic sensors, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase and sirtuin (SIRT) 1. Furthermore, it significantly increased glucose uptake by enhancing glucose consumption and subsequently decreased FFA contents and increased carnitine palmitoyltransferase (CPT) 1b expression. Our study indicates that ARA has a potential for stimulating mitochondrial function and energy metabolism in muscle.

Nonalcoholic Steatohepatitis (NASH) in OB/OB Mice Treated with Yo Jyo Hen Shi Ko (YHK): Effects on Peroxisome Proliferator-Activated Receptors (PPARs) and Microsomal Triglyceride Transfer Protein (MTP)

2007 ◽  
Vol 52 (12) ◽  
pp. 3448-3454 ◽  
Author(s):  
José Tadeu Stefano ◽  
Claudia Pinto Marques Souza de Oliveira ◽  
Maria Lúcia Corrêa-Giannella ◽  
Vicência Mara Rodrigues de Lima ◽  
Sandra Valéria de Sá ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Microsomal Triglyceride Transfer Protein ◽  
Peroxisome Proliferator ◽  
Transfer Protein ◽  
Peroxisome Proliferator Activated Receptors
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