Effects of insulin on pharmacodynamics of immunosuppressive drugs in human peripheral T lymphocytes

Research Project

Project/Area Number	15K08081
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Medical pharmacy
Research Institution	Tokyo University of Pharmacy and Life Science
Principal Investigator	Hirano Toshihiko 東京薬科大学, 薬学部, 教授 (90173252)
Research Collaborator	杉山健太郎東京薬科大学, 薬学部, 准教授
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	腎移植 / インスリン / 末梢血単核細胞（PBMC） / 免疫抑制薬 / 慢性腎不全患者 / 薬物耐性 / 個別医療 / 副腎皮質ステロイド薬 / 末梢血単核細胞 / 単球 / インスリン受容体 / ヒト末梢血単核細胞 / グルココルチコイド / 慢性腎不全 / T細胞増殖 / シクロスポリン / タクロリムス / ミコフェノール酸
Outline of Final Research Achievements	Diabetes mellitus is one of the most common causes of chronic renal failure. Clinical efficacies of immunosuppressive drugs are possibly affected by insulin after renal transplantation. We investigated the effects of insulin on responses of mitogen-activated human peripheral-blood mononuclear cells (PBMCs) to several immunosuppressive drugs. The IC50 values of immunosuppressive drugs against the mitogen-activated PBMCs in the presence of insulin were significantly higher than those of the drug without insulin (P<0.05). Insulin receptors were detected on the mitogen-activated CD4+/CD14+ cells in PBMCs. insulin-receptor antagonist recovered the effect of immunosuppressive drugs. These results indicate that insulin attenuates suppressive efficacies of immunosuppressive drugs against mitogen-activated proliferation of human PBMCs, possibly via insulin receptors. Insulin used in patients accompanying diabetes mellitus is suggested to attenuate efficacies of immunosuppressive drugs.