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According to this concept, a T\u2010helper lymphocyte of type 1 (Th1) subset of T\u2010lymphocytes and their cytokine products, the type 1 cytokines [<jats:italic>e.g.<\/jats:italic> interleukin 2 (IL\u20102), interferon gamma (IFN\u2010\u03b3) and tumour necrosis factor beta (TNF\u2010\u03b2)] prevail over immunoregulatory (anti\u2010inflammatory) Th2 subset and its cytokine products, <jats:italic>i.e<\/jats:italic>. type 2 cytokines (<jats:italic>e.g<\/jats:italic>. IL\u20104, IL\u20106 and IL\u201010). This allows type 1 cytokines to initiate a cascade of immune\/inflammatory processes in the islet (insulitis), culminating in \u03b2\u2010cell destruction. Activation of sympathetic\u2010corticotropin\u2010releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor <jats:sc>L<\/jats:sc>\u2010arginine supply for nitric oxide (NO)\u2010assisted insulin secretion. This determines the shift of intraislet glutamate metabolism from the synthesis of glutathione (GSH) to that of <jats:sc>L<\/jats:sc>\u2010arginine, leading to a redox imbalance that activates nuclear factor \u03baB exacerbating inflammation and NO\u2010mediated cytotoxicity. Physical exercise is capable of inducing changes in the pattern of cytokine production and release towards type 2 class and to normalize the glutamine supply to the circulation, which reduces the need for glutamate, whose metabolic fate may be restored in the direction of GSH synthesis and antioxidant defence. Also, the 70\u2010kDa heat shock protein (hsp70), which is immunoregulatory, may modulate exercise\u2010induced anti\u2010inflammation. In this work, we envisage how exercise can intervene in the mechanisms involved in the autoimmune process against \u03b2\u2010cells and how novel therapeutic approaches may be inferred from these observations. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cbf.1470","type":"journal-article","created":{"date-parts":[[2008,3,31]],"date-time":"2008-03-31T06:46:27Z","timestamp":1206945987000},"page":"406-433","source":"Crossref","is-referenced-by-count":49,"title":["Type 1 diabetes: can exercise impair the autoimmune event? The <scp>L<\/scp>\u2010arginine\/glutamine coupling hypothesis"],"prefix":"10.1002","volume":"26","author":[{"given":"Maur\u00edcio","family":"da Silva Krause","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Paulo Ivo Homem","family":"de Bittencourt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,3,31]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025160614313"},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0065-3101(24)00176-2","article-title":"The predictability of insulin\u2010dependent diabetes mellitus?","volume":"35","author":"Riley WJ","year":"1988","journal-title":"Adv Pediatr"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.30.1.26"},{"key":"e_1_2_1_6_2","first-page":"271","article-title":"Anti\u2010thymocyte globulin and prednisone immunotherapy of recent onset type 1 diabetes mellitus?","volume":"2","author":"Eisenbarth GS","year":"1985","journal-title":"Diabetes Res"},{"key":"e_1_2_1_7_2","first-page":"709","article-title":"Result of 3 years of screening for preclinical phase of juvenile insulin\u2010dependent diabetes mellitus?","volume":"47","author":"Lesage C","year":"1990","journal-title":"Arch Fr Pediatr"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1365"},{"key":"e_1_2_1_9_2","first-page":"48","article-title":"Exhaustive exercise and type\u20101\/type\u20102 cytokine balance with special focus on interleukin\u201012 p40\/p70?","volume":"9","author":"Suzuki K","year":"2003","journal-title":"Exerc Immunol Rev"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-15-4-516"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00492-9"},{"key":"e_1_2_1_12_2","first-page":"110","article-title":"Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited?","volume":"4","author":"Kloppel G","year":"1985","journal-title":"Surv Synth Pathol Res"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100021"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/1056-8727(94)90009-4"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.001045"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90044-L"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000236199"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-75741-9_9"},{"key":"e_1_2_1_19_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2337\/diab.41.8.897","article-title":"Does nitric oxide mediate autoimmune destruction of \u03b2\u2010cells? 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