scholarly journals RAPID COMMUNICATION: Inhibitory Effect of Pioglitazone on Carotid Arterial Wall Thickness in Type 2 Diabetes

2001 ◽  
Vol 86 (7) ◽  
pp. 3452-3452 ◽  
Author(s):  
Hiroyuki Koshiyama ◽  
Dai Shimono ◽  
Naomitsu Kuwamura ◽  
Jun Minamikawa ◽  
Yoshio Nakamura
Keyword(s):  
Type 2 Diabetes ◽  
Statistical Significance ◽  
Intima Media Thickness ◽  
Inhibitory Effect ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Carotid Arterial

There have been increasing evidences that thiazolidinediones, peroxisome proliferator-activated receptor γ (PPARγ) agonists, may have some antiatherogenic actions. We have previously reported that troglitazone has a potent inhibitory effect on common carotid arterial intima-media thickness (IMT) in subjects with type 2 diabetes. However, some studies suggested a possibility that PPARγ activators may have protoatherogenic actions, raising concern about their detrimental effects in diabetic subjects. In the present study, we investigated the effect of treatment with pioglitazone, another PPARγ agonist, on IMT in a total of 106 Japanese subjects with type 2 diabetes. Pioglitazone (30 mg daily) was administered for 6 months in 53 patients. Compared to control group (n = 53), the group given pioglitazone showed a significant decrease in IMT as early as 3 months after the administration. The decrease in IMT was also found after 6 months (IMT change: −0.084[SE 0.023] mm vs. control 0.022[SE 0.006] mm, P < 0.001), although the difference between those after 3 and 6 months did not reach any statistical significance. These findings indicate that thiazolidinediones cause an inhibition of early atherosclerotic process PPARγ activation.

scholarly journals Correlation between PPARGC1A gene rs8192678 G>A polymorphism and susceptibility to type-2 diabetes

2019 ◽  
Vol 14 (1) ◽  
pp. 43-52
Author(s):  
Fei Du ◽  
Kang-Juan Yang ◽  
Lian-Shan Piao
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Genetic Models ◽  
Cochrane Library ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Case Control Studies ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inheritance Model

AbstractObjectiveTo systematically investigate the correlation between the G>A polymorphism of the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A or PGC-1alpha) gene rs8192678 locus and the susceptibility to type-2 diabetes mellitus (T2DM).MethodsThe inclusion and exclusion criteria and retrieval strategies of original literatures were formulated. Then, subjects and free words “PPARGC1A”,”gene polymorphism”, and “T2DM” were retrieved from the PubMed, EMBASE, and Cochrane Library databases. Case-control studies on the G>A polymorphism of the PPARGC1A gene rs8192678 locus and susceptibility to T2DM were included for the meta-analysis.ResultsThe number of cases in the T2DM group and control group was 5,607 and 7,596, respectively. The meta-analysis revealed that the PPARGC1A gene rs8192678 locus G>A polymorphism is associated with susceptibility to T2DM. There are differences in each group of genetic models, of which three groups of genetic models are highly significant. In the allele model, OR=1.249, 95% CI: 1.099-1.419, and P=0.001. In the dominant inheritance model, OR=1.364, 95% CI: 1.152-1.614, and P=0.000. In the additive inheritance model, OR=0.828, 95% CI: 0.726-0.945, and P=0.005. And one group is significant, in the recessive inheritance model, OR=1.187, 95% CI: 1.021-1.381, and P=0.026.ConclusionIn Western Asian, South Asian, European and African populations, the A allele of the PPARGC1A gene rs8192678 locus may be one of the risk factors for T2DM.

Pioglitazone prevents cardiac remodeling in high-fat, high-calorie-induced Type 2 diabetes mellitus

2006 ◽  
Vol 291 (1) ◽  
pp. H81-H87 ◽  
Author(s):  
Walter E. Rodriguez ◽  
Irving G. Joshua ◽  
Jeff C. Falcone ◽  
Suresh C. Tyagi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Left Ventricular ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Calorie Diet

The agonists of peroxisome proliferator-activated receptor-γ (PPARγ) ameliorate cardiovascular complications associated with diabetes mellitus. We tested the hypothesis that recovery from ailing to failing myocardium in diabetes by PPARγ agonist is in part due to decreased matrix metalloproteinase-9 (MMP-9) activation and left ventricular (LV) tissue levels of homocysteine (Hcy). C57BL/6J mice were made diabetic (D) by feeding them a high-fat calorie diet. PPARγ was activated by adding pioglitazone (Pi) to the diet. After 6 wk, mice were grouped into: normal calorie diet (N), D, N + Pi and D + Pi ( n = 6 in each group). LV variables were measured by echocardiography, endothelial-myocyte (E-M) coupling was measured in cardiac rings, and MMP-9 activation was measured by zymography. Blood glucose levels were twofold higher in D mice compared with N mice. Pi decreased the levels of glucose in D mice to the levels in N mice. LV Hcy levels were 3.5 ± 0.5 μM in N groups compared with 12.4 ± 0.6 μM in D groups. Treatment with Pi normalized the LV levels of Hcy but had no effect on plasma levels of Hcy. In the D group, LV contraction was reduced compared with that of the N group and was ameliorated by treatment with Pi. LV wall thickness was reduced to 0.25 ± 0.02 mm in the D group compared with 0.42 ± 0.01 mm in the N group. LV diastolic diameter was 3.05 ± 0.01 mm in the D group compared with 2.20 ± 0.02 mm in the N group. LV systolic diameter was 1.19 ± 0.02 mm in the D group and 0.59 ± 0.01 mm in the N group. Pi normalized the LV variables in D mice. The responses to ACh and nitroprusside were attenuated in diabetic hearts, suggesting that there was E-M uncoupling in the D group compared with the N group, which was ameliorated by Pi. Plasma and LV levels of MMP-2 and -9 activities were higher in the D group than in the N group but normalized after Pi treatment. These results suggest that E-M uncoupling in the myocardium, in part, is due to increased MMP activities secondary to suppressing PPARγ activity in high-fat, calorie-induced Type 2 diabetes mellitus.

scholarly journals PPARγAgonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Sun ◽  
Zhanjun Jia ◽  
Gang Liu ◽  
Li Zhou ◽  
Mi Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Glomerular Injury ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Expressions ◽  
Pg E2 ◽  
Cox 1

Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)γand PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPARγactivation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN.

The PROactive and DREAM Studies

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Roy Taylor
Keyword(s):  
Type 2 Diabetes ◽  
Ace Inhibitor ◽  
Preventive Treatment ◽  
Peroxisome Proliferator ◽  
Converting Enzyme ◽  
Abnormal Glucose Tolerance ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Rate Of Progression

These two large studies, PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) and Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM), had very different aims. PROactive asked whether the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone could decrease macrovascular morbidity and mortality in people with type 2 diabetes who were already taking maximum preventive treatment.1DREAM asked whether rosiglitazone and ramipril (PPARγ agonist and angiotensin-converting enzyme (ACE) inhibitor, respectively), either in combination or individually, could decrease the rate of progression to diabetes in people with abnormal glucose tolerance.2,3

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