Unique ID issued by UMIN | UMIN000004189 |
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Receipt number | R000005033 |
Scientific Title | Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages |
Date of disclosure of the study information | 2010/09/15 |
Last modified on | 2013/09/12 17:33:05 |
Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages
Pioglitazone and cholesterol efflux
Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages
Pioglitazone and cholesterol efflux
Japan |
Diabetes
Endocrinology and Metabolism |
Others
NO
To investigate whether pioglitazone enhance cholesterol efflux and ABCA1/G1 expressions in macrophages, we plan to obtain blood from diabetic patients before and after orally administtation of pioglitazone, and compare them.
Efficacy
Macrophage ABCA1/G1 expressions and cholesterol efflux cultured under sera obtained from diabetic patients
Interventional
Cross-over
Randomized
Open -but assessor(s) are blinded
Placebo
2
Treatment
Medicine |
Oral administration of pioglitazone
Oral administration of placebo
20 | years-old | <= |
75 | years-old | >= |
Male and Female
Type 2 diabetic patients who are treated with piogliitazone at least for 6 months and have good tolerance without relevant side effects
Poor-controlled diabetes (HbA1c>8.0 %)
15
1st name | |
Middle name | |
Last name | Katsunori Ikewaki |
National Defense Medical College
Department of Internal Medicine I
3-2 Namiki, Tokorozawa, JAPAN 359-8513
04-2995-1597
katsunorike@ndmc.ac.jp
1st name | |
Middle name | |
Last name | Makoto Ayaori |
National Defense Medical College I
Department of Internal Medicine
3-2 Namiki, Tokorozawa, JAPAN 359-8513
04-2995-1597
ayaori@ndmc.ac.jp
National Defense Medical College
Foundation for Promotion of Defense Medicine
Non profit foundation
NO
2010 | Year | 09 | Month | 15 | Day |
Published
http://www.sciencedirect.com/science/article/pii/S0021915011007349
Objective
Pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist, reportedly reduces cardiovascular events in diabetic patients. ATP cassette binding transporters (ABC) A1 and G1 are pivotal molecules for cholesterol efflux (ChE) from macrophages and high density lipoprotein biogenesis, and the A1 transporter is regulated by a PPARgamma-liver receptor X (LXR) pathway. Also, pioglitazone induces ABCG1 expression, though the exact mechanism remains unclear. We therefore investigated the effects of pioglitazone on ABCA1/G1 expression in vitro and ex vivo.
Methods
The effects of pioglitazone on ChE and ABCA1/G1 expressions inmacrophages were assessed. Then, mRNA was quantified in macrophages when PPARgamma/LXR inhibition by siRNA or overexpression of oxysterol sulfotransferase was performed. ABCA1/G1 promoter activity with mutated LXR-responsive elements was also measured. As an ex vivo study, 15 type 2 diabetic patients were administered pioglitazone or placebo, and ChE assays and protein expressions were determined using macrophages cultured with the corresponding sera.
Results
Pioglitazone increased LXRalpha/ABCA1/G1 expressions, which enhanced ChE from macrophages. Inhibition of PPARgamma/LXR pathways revealed that LXR was primarily involved in pioglitazone's transactivation of ABCA1 but only partially involved for ABCG1. Promoter assays showed that ABCG1 was regulated more by the promoter in intron 4 than that upstream of exon 1 but both promoters were responsive to LXR activation. Sera obtained after pioglitazone treatment promoted ChE and ABCA1/G1 expressions in macrophages.
Conclusion
Pioglitazone enhanced ChE from macrophages by increasing ABCA1/G1 in LXR-dependent and -independent manners. Our comparable in vitro and ex vivo results shed new light on pioglitazone's ovel anti-atherogenic property.
Terminated
2010 | Year | 08 | Month | 10 | Day |
2010 | Year | 09 | Month | 01 | Day |
2010 | Year | 09 | Month | 10 | Day |
2013 | Year | 09 | Month | 12 | Day |
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005033
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