title: Insulin promotes T cell recovery in a murine model of autoimmune myocarditis.
abstract: Glucose-insulin-potassium (GIK) is a useful adjunct to myocarditis. Besides its essential action in energy metabolism, insulin also exerts an anti-inflammatory effect. This study investigated the effect of insulin on myocardial inflammation in experimental autoimmune myocarditis (EAM) in mice and its potential role in T cell regulation. Mice were divided randomly into a normal control group, a saline-treated EAM group and an insulin-treated EAM group. The histopathological changes of myocardium, α-myosin heavy chain (MyHCα)(614-629) antigen-specific autoantibody titre, the serum level of cardiac troponin I (cTnI), mitogen-activated protein kinase (MAPK) family members' activity and content were measured. Furthermore, the phenotype of T lymphocyte subsets in splenocytes was analysed to evaluate the immune status of mice. Insulin reduced serum cTnI of EAM mice on days 14 and 21 (P < 0·05) after immunization, with no changes in blood glucose and autoantibody production. Western blot revealed that extracellular signal-regulated protein kinase (ERK1/2) may be a determining factor in this process. Total ERK1/2 and phospho-ERK1/2 (p-ERK1/2) were both up-regulated in insulin-treated mice after immunization. We also found that insulin treatment promoted T cell recovery without changing the naive-to-memory T-cell ratio; in particular, CD3(+) T cells in insulin-treated mice proliferated more vigorously than in control mice (P < 0·05). We report here for the first time that insulin alleviates myocarditis in the EAM model. These data show that insulin has a direct effect on T cell proliferation in EAM. It is possible that GIK or insulin may assist T cell recovery towards normal in myocarditis, especially for diabetic or hyperglycaemic patients.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Zhuang
authors.forename: C
authors.initials: C
authors.lastname: Geng
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: W
authors.initials: W
authors.lastname: Lei
authors.forename: N
authors.initials: N
authors.lastname: Tian
authors.forename: F
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D001786:Blood Glucose / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D004195:Disease Models, Animal; D007328:Insulin / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019210:Troponin I / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects; D024723:Ventricular Myosins / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D017252:CD3 Complex; D007328:Insulin; D019210:Troponin I; D020928:Mitogen-Activated Protein Kinases; D024723:Ventricular Myosins