Additive and Antagonistic Effects Among Combination of Agonists of Peroxisome Proliferator-Activated Receptor gamma (PPARg) on Transcriptional Activity
Journal Title: Diabetes Research – Open Journal - Year 2015, Vol 1, Issue 2
Abstract
Objective: The Angiotensin-II receptor blocker telmisartan and sulfonylurea glimepiride may have clinical usefulness as partial agonists of PPARg. We investigated additive and antagonistic effects among combinations of telmisartan, glimepiride, and the Thiazolidinedione (TZD) selective PPARg agonist pioglitazone on transcriptional activity of PPARg. Materials/Methods: The receptors of pCMX-PPARg and pCMX-RXR, and PPRE-Luc reporter gene were transfected into CV1 cells, and treated with following agents, and luciferace assay was performed. Moreover, mammalian two-hybrid assay was done using GAL4 responsive reporter tk-MH100(UAS)×4-Luc and the chimeric receptor GAL4-PPARg. Results: Telmisartan increased transactivation of PPARg dose dependently. Activation by telmisartan 10 µM was 58.8% of that by pioglitazone 10 µM. Glimepiride also increased transactivation of PPARg dose dependently. Activation by glimepiride 10 µM was 49.8% of that by pioglitazone 10 µM. Addition of telmisartan 5 µM significantly enhanced transactivation by glimepiride 10 and 50 µM. Moreover, addition of pioglitazone 0.5 µM significantly enhanced transactivation by glimepiride 10 and 50 µM. Mammalian two-hybrid assay showed additive effect between glimepiride and telmisartan on binding of SRC-1 to PPARg. On the other hand, addition of glimepiride 10 and 50 µM reduced transactivation by pioglitazone 5 µM to 74% and 70%, respectively. Conclusion: Partial agonists of PPARg additively enhanced transactivation by other agonists, whereas high concentration of partial agonists reduced transactivation by full agonist antagonistically.
Authors and Affiliations
Daisuke Tsuriya
Keywords
Related Articles
- EP ID EP550007
- DOI 10.17140/DROJ-1-105
- Views 157
- Downloads 0
Study of the Central and Peripheral Autonomic Function in Short Evolutions Type 2 Diabetes and it’s Risk Categories
for type 2 diabetes (prediabetes) to recently established type 2 diabetes. Research Design and Methods: It is a longitudinal, prospective and observational study (population consisting in 30 control subjects, 30 patients...
Current Controversies around Carbohydrate Restriction and the Risk of High-Protein Diets
Recently, a Low carbohydrate (LCH) diet has been recommended by many doctors to control hyperglycemia and overweight. Unlike a traditional calorie-restricted diet, a carbohydrate-restricted diet typically contains less t...
Substitution of Chronic Insulin Therapy with Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-transporter-2 Inhibitors
Insulin is a very useful and widely used treatment for diabetes. Temporary insulin therapy improves glucose toxicity due to improved β-cell function of the pancreas. Upon achieving glycemic control, insulin treatment cou...
Publishing Research: From an Occupational Therapy Perspective
Two years ago, at the inception of this Diabetes Research – Open Journal, I wrote an opinion article for the inaugural issue about the need for articles targeting secondary prevention.1 The journal has grown to provide m...
Clinical and Experimental Evidence of Hypoglycemic Neuropathy
When compared with the extensive research on hypoglycemic impacts on Central Nervous System (CNS) and cardiovascular system, the effects of hypoglycemia on the Peripheral Nervous System (PNS) have not been investigated a...