Kim MS, Polychronakos C. Immunogenetics of type 1 diabetes. Horm Res. 2005;64(4):180–8.

CAS  PubMed  Google Scholar 

Jahromi MM, Eisenbarth GS. Cellular and molecular pathogenesis of type 1A diabetes. Cell Mol Life Sci. 2007;64(7–8):865–72.

Article  CAS  PubMed  Google Scholar 

Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and Β-cell loss in type 1 diabetes. Nat Rev Endocrinol. 2009;5(4):219–26.

Article  CAS  PubMed  Google Scholar 

De Beeck AO, Eizirik DL. Viral infections in type 1 diabetes mellitus-why the β cells? Nat Rev Endocrinol. 2016;12(5):263–73.

Article  PubMed Central  Google Scholar 

DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018;391(10138):2449–62.

Article  PubMed  PubMed Central  Google Scholar 

Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of jdrf, the endocrine society, and the American diabetes association. Diabetes Care. 2015;38(10):1964–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pirot P, Cardozo AK, Eizirik DL. Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes. Arq Bras Endocrinol Metabol. 2008;52(2):156–65.

Article  PubMed  Google Scholar 

von Herrath M, Christoffersson G, Rodriguez-Calvo T. Recent advances in understanding type 1 diabetes. F1000Res. 2016;5:1–8.

Google Scholar 

Eizirik DL, Pasquali L, Cnop M. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure. Nat Rev Endocrinol. 2020;16(7):349–62.

Article  CAS  PubMed  Google Scholar 

Ortis F, Cardozo AK, Crispim D, Störling J, Mandrup-Poulsen T, Eizirik DL. Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-κB activation. Mol Endocrinol. 2006;20(8):1867–79.

Article  CAS  PubMed  Google Scholar 

Ortis F, Pirot P, Naamane N, Kreins AY, Rasschaert J, Moore F, et al. Induction of nuclear factor-κB and its downstream genes by TNF-α and IL-1β has a pro-apoptotic role in pancreatic beta cells. Diabetologia. 2008;51(7):1213–25.

Article  CAS  PubMed  Google Scholar 

Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science  (80-). 2011;334(6059):1081–6.

Article  CAS  Google Scholar 

Meyerovich K, Ortis F, Allagnat F, Cardozo AK. Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. J Mol Endocrinol. 2016;57(1):R1-17.

Article  CAS  PubMed  Google Scholar 

Brozzi F, Nardelli TR, Lopes M, Millard I, Barthson J, Igoillo-Esteve M, et al. Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms. Diabetologia. 2015;58(10):2307–16.

Article  CAS  PubMed  Google Scholar 

Cardozo AK, Heimberg H, Heremans Y, Leeman R, Kutlu B, Kruhøffer M, et al. A comprehensive analysis of cytokine-induced and nuclear factor-κB-dependent genes in primary rat pancreatic β-cells. J Biol Chem. 2001;276(52):48879–86.

Article  CAS  PubMed  Google Scholar 

Cardozo AK, Ortis F, Storling J, Feng Y, Rasschaert J, Tonnesen M, Van Eylen F, Mandrup-Poulsen T, Herchuelz AED. Cytokines downregulate the sarcoendoplasmic endoplasmic reticulum Ca2h, leading to induction of reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum stress in pancreatic β-Cells. Diabetes. 2005;54:452–61.

Article  CAS  PubMed  Google Scholar 

Lu X, Zhao C. Exercise and type 1 diabetes. Adv Exp Med Biol. 2020;1228(107):107–21.

Article  CAS  PubMed  Google Scholar 

Litchfield I, Andrews RC, Narendran P, Greenfield S. Patient and healthcare professionals perspectives on the delivery of exercise education for patients with type 1 diabetes. Front Endocrinol (Lausanne). 2019;10:1–13.

Article  Google Scholar 

Valerio G, Spagnuolo MI, Lombardi F, Spadaro R, Siano M, Franzese A. Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2007;17(5):376–82.

Article  PubMed  Google Scholar 

Pedersen BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem. 2006;42:105–17.

Article  CAS  PubMed  Google Scholar 

Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993–1017.

Article  CAS  PubMed  Google Scholar 

Muñoz VR, Gaspar RC, Kuga GK, da Rocha AL, Crisol BM, Botezelli JD, et al. Exercise increases Rho-kinase activity and insulin signaling in skeletal muscle. J Cell Physiol. 2018;233(6):4791–800.

Article  PubMed  Google Scholar 

Huang HH, Farmer K, Windscheffel J, Yost K, Power M, Wright DE, et al. Exercise increases insulin content and basal secretion in pancreatic islets in type 1 diabetic mice. Exp Diabetes Res. 2011;2011(1):481427.

PubMed  PubMed Central  Google Scholar 

Paula FMM, Leite NC, Vanzela EC, Kurauti MA, Freitas-Dias R, Carneiro EM, et al. Exercise increases pancreatic β-cell viability in a model of type 1 diabetes through IL-6 signaling. FASEB J. 2015;29(5):1805–16.

Article  CAS  PubMed  Google Scholar 

Paula FMM, Leite NC, Borck PC, Freitas-Dias R, Cnop M, Chacon-Mikahil MPT, et al. Exercise training protects human and rodent β cells against endoplasmic reticulum stress and apoptosis. FASEB J. 2018;32(3):1524–36.

Article  CAS  PubMed  Google Scholar 

John SR. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol. 2018;10:a028415. https://doi.org/10.1101/cshpersect.a028415.

Kang S, Narazaki M, Metwally H, Kishimoto T. Historical overview of the interleukin-6 family cytokine. J Exp Med. 2020;217(5):1–10.

CAS  Google Scholar 

Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKβ and ER stress inhibition. PLoS Biol. 2010;8(8):31–2.

Article  Google Scholar 

Belotto MF, Magdalon J, Rodrigues HG, Vinolo MAR, Curi R, Pithon-Curi TC, et al. Moderate exercise improves leucocyte function and decreases inflammation in diabetes. Clin Exp Immunol. 2010;162(2):237–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379–406.

Article  CAS  PubMed  Google Scholar 

Kang S, Tanaka T, Narazaki M, Kishimoto T. Targeting interleukin-6 signaling in clinic. Immunity. 2019;50(4):1007–23.

Article  CAS  PubMed  Google Scholar 

Engin F, Yermalovich A, Ngyuen T, Hummasti S, Fu W, Eizirik DL, et al. Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes. Sci Transl Med. 2013;5(211):211ra156.

Article  PubMed  PubMed Central  Google Scholar 

Cadavez L, Montane J, Alcarraz-Vizán G, Visa M, Vidal-Fàbrega L, Servitja JM, et al. Chaperones ameliorate beta cell dysfunction associated with human islet amyloid polypeptide overexpression. PLoS ONE. 2014;9(7):1–11.

Article  Google Scholar 

Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium efflux from the endoplasmic reticulum leads to β-cell death. Endocrinology. 2014;155(3):758–68.

Article  CAS  PubMed  Google Scholar 

Allagnat F, Fukaya M, Nogueira TC, Delaroche D, Welsh N, Marselli L, et al. C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells. Cell Death Differ. 2012;19(11):1836–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eldor R, Yeffet A, Baum K, Doviner V, Amar D, Ben-Neriah Y, et al. Conditional and specific NF-κB blockade protects pancreatic beta cells from diabetogenic agents. Proc Natl Acad Sci U S A. 2006;103(13):5072–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Biol. 2013;14(10):630–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hwang J, Qi L. Quality control in the endoplasmic reticulum: crosstalk between ERAD and UPR pathways. Trends Biochem Sci. 2018;43(8):593–605.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu Q, Zhong JJ, Jin JF, Yin XM, Miao H. Tauroursodeoxycholate, a chemical chaperone, prevents palmitate-induced apoptosis in pancreatic β-cells by reducing ER stress. Exp Clin Endocrinol Diabetes. 2013;121(1):43–7.

CAS