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 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.

Improvement of glucose and lipid metabolism in diabetic rats treated with molybdate

1996 ◽  
Vol 270 (2) ◽  
pp. E344-E352 ◽  
Author(s):  
A. T. Ozcelikay ◽  
D. J. Becker ◽  
L. N. Ongemba ◽  
A. M. Pottier ◽  
J. C. Henquin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Diabetic Rats ◽  
Nonesterified Fatty Acids ◽  
Insulin Resistant ◽  
Hepatic Glucose Metabolism ◽  
Glucose And Lipid Metabolism ◽  
Glycogen Stores

Molybdenum mimics certain insulin actions in vitro. We have investigated the effects of oral administration of Na2MoO4 (Mo) for 8 wk on carbohydrate and lipid metabolism in streptozotocin-diabetic rats. Mo decreased hyperglycemia and glucosuria by 75% and corrected the elevation of plasma nonesterified fatty acids. Tolerance to glucose loads was improved, and glycogen stores were replenished. These effects were not due to a rise of insulinemia. In liver, Mo restored the blunted mRNA and activity of glucokinase and pyruvate kinase and decreased to normal phosphoenolpyruvate carboxykinase values. Finally, Mo totally reversed the low expression and activity of acetyl-CoA carboxylase and fatty acid synthase in liver, but not in white adipose tissue. In conclusion, Mo exerts a marked blood glucose-lowering effect in diabetic rats by an insulin-like action. This effect results in part from a restoration of hepatic glucose metabolism and is associated with a tissue-specific correction of lipogenic enzyme gene expression, both processes being essentially mediated by reversal of impaired pretranslational regulatory mechanisms. These observations raise new therapeutic perspectives in diabetes, particularly in the insulin-resistant condition.

Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats

2000 ◽  
Vol 278 (1) ◽  
pp. H256-H262 ◽  
Author(s):  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Kinya Otsu ◽  
Tsunehiko Kuzuya ◽  
Masatsugu Hori
Keyword(s):  
Infarct Size ◽  
Myocardial Injury ◽  
Coronary Occlusion ◽  
Plasma Cholesterol ◽  
Diabetic Rats ◽  
Total Plasma Cholesterol ◽  
Total Plasma ◽  
Cholesterol Feeding ◽  
Insulin Dependent ◽  
Zdf Rats

We measured infarct size after coronary occlusion (30 min) and reperfusion (24 h) in genetic non-insulin-dependent Zucker diabetic fatty (ZDF) rats with and without 4-wk cholesterol feeding. Infarct size was similar in ZDF rats and lean control rats but was significantly larger in cholesterol-fed diabetic rats than in cholesterol-fed lean rats ( P < 0.05). Plasma levels of glucose, insulin, and triglycerides were significantly higher in diabetic rats and were not influenced by cholesterol feeding. The increase in total plasma cholesterol induced by cholesterol feeding was significantly greater in diabetic rats than in lean rats ( P < 0.05). A significant positive correlation was found between total plasma cholesterol and infarct size ( P < 0.05). Myeloperoxidase activity, as an index of neutrophil accumulation, was significantly higher and expression of P-selectin was more marked in the ischemic myocardium of cholesterol-fed diabetic rats than of cholesterol-fed lean rats. Acetylcholine-induced endothelium-dependent relaxation (EDR) of aortic rings was markedly impaired in cholesterol-fed diabetic rats. Thus cholesterol feeding significantly exacerbated myocardial injury produced by coronary occlusion-reperfusion in non-insulin-dependent diabetic rats, possibly because of enhanced expression of P-selectin and impairment of EDR in the coronary bed.

scholarly journals Kinetic study of the expression of genes related to hepatic steatosis, glucose and lipid metabolism, and cellular stress during overfeeding in mule ducks

2020 ◽  
Vol 318 (2) ◽  
pp. R453-R467 ◽  
Author(s):  
Tracy Pioche ◽  
Fabien Skiba ◽  
Marie-Dominique Bernadet ◽  
Iban Seiliez ◽  
William Massimino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Cellular Stress ◽  
Liver Weight ◽  
Cell Protection ◽  
Glucose And Lipid Metabolism ◽  
Potential Biomarker ◽  
Cholesterol Biosynthetic Pathway

Induced by overfeeding, hepatic steatosis is a process exploited for the “foie gras” production in mule ducks. To better understand the mechanisms underlying its development, the physiological responses of mule ducks overfed with corn for a duration of 11 days were analyzed. A kinetic analysis of glucose and lipid metabolism and cell protection mechanisms was performed on 96 male mule ducks during overfeeding with three sampling times (after the 4th, the 12th, and the 22nd meal). Gene expression and protein analysis realized on the liver, muscle, and abdominal fat showed an activation of a cholesterol biosynthetic pathway during the complete overfeeding period mainly in livers with significant correlations between its weight and its cholesterolemia ( r = 0.88; P < 0.0001) and between the liver weight and the hmgcr and soat1 expression ( r = 0.4, P < 0.0001 and r = 0.67; P < 0.0001, respectively). Results also revealed an activation of insulin and amino acid cells signaling a pathway suggesting that ducks boost insulin sensitivity to raise glucose uptake and use via glycolysis and lipogenesis. Cellular stress analysis revealed an upregulation of key autophagy-related gene expression atg8 and sqstm1( P < 0.0001) during the complete overfeeding period, mainly in the liver, in contrast to an induction of cyp2e1( P < 0.0001), suggesting that autophagy could be suppressed during steatosis development. This study has highlighted different mechanisms enabling mule ducks to efficiently handle the starch overload by keeping its liver in a nonpathological state. Moreover, it has revealed potential biomarker candidates of hepatic steatosis as plasma cholesterol for the liver weight.

Effect of Aqueous Extract of Phaseolus Vulgaris on the Regulation of Glucose and Lipid Metabolism in Diabetic Rats

2017 ◽  
Vol 03 (01) ◽  
pp. 43-49
Author(s):  
Louise Anin Anin Atchibri ◽  
Lêniféré Chantal Soro ◽  
Jean Jacques Diagou ◽  
Dago Gnakri
Keyword(s):  
Lipid Metabolism ◽  
Phaseolus Vulgaris ◽  
Aqueous Extract ◽  
Diabetic Rats ◽  
Glucose And Lipid Metabolism
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