title: Rapamycin/GABA combination treatment ameliorates diabetes in NOD mice.
abstract: Type 1 diabetes (T1D) is one of the most common autoimmune diseases, affecting nearly 20 million people worldwide. The pathogenesis of T1D is characterized by the progressive destruction of insulin-producing pancreatic β-cells by autoreactive T cells. The significant role of immunomodulation in preserving residual insulin-producing β-cells in newly diagnosed T1D has not been confirmed yet. However, a combination of treatments acting via distinct mechanisms is widely considered to be the most promising future therapeutic approach in this respect. Rapamycin and gamma-aminobutyric acid (GABA) administration alone showed no effects on late-stage disease. By contrast, combined rapamycin/GABA treatment effectively suppressed autoimmune responses to islet cells and improved islet function in recent-onset diabetes. In particular, after the onset of hyperglycemia, those treated with the rapamycin/GABA combination showed significant amelioration of diabetes amelioration compared to those treated with either rapamycin or GABA alone. This protective effect of the rapamycin/GABA combination treatment in nonobese diabetic (NOD) mice was exerted through two distinct mechanisms. Rapamycin induced regulatory T cells and consequently suppressed targeted autoimmune responses to islet cells, which may be relevant to the reduced insulitis observed in rapamycin-treated NOD mice. By contrast, treatment with GABA improved islet function in diabetic NOD mice. We believe that our observations are highly relevant to establishing clinical strategies for the prevention and treatment of T1D in future.
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Sirong
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Hepatobiliopancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiration Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Cell Transplantation (Seventh Unit of General Surgery Department), Institute of Organ Transplantation, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072，PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: chenquan@cqmu.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D060888:Real-Time Polymerase Chain Reaction; D020123:Sirolimus / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D005680:gamma-Aminobutyric Acid; D020123:Sirolimus
keywords: Autoimmune diabetes; GABA; Rapamycin