A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients
| Autor: | Jin-Fang Song, Temitope Isaac Adelusi, Wei Li, Jing Zhu, Zhenhai Shang, Qian Lu, Xiaoxing Yin, Sun Juan, Dongmei Lv, Tao Wang, Xueyan Zhou, Zejun Bao, Yan Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male China endocrine system diseases medicine.medical_treatment 030209 endocrinology & metabolism Type 2 diabetes Pharmacology Article 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Insulin resistance Asian People Piperidines Diabetes mellitus Medicine Humans Protein kinase B Multidisciplinary Polymorphism Genetic business.industry Akt/PKB signaling pathway Insulin Type 2 Diabetes Mellitus Hep G2 Cells Middle Aged medicine.disease Repaglinide 030104 developmental biology Diabetes Mellitus Type 2 KCNQ1 Potassium Channel Insulin Receptor Substrate Proteins Female Carbamates Insulin Resistance business Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536). |
| Databáze: | OpenAIRE |
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