Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting ß-cell regeneration

Couri, Carlos Eduardo Barra; Foss, Milton César; Voltarelli, Júlio César

doi:10.1590/s0100-879x2006001000002

Cited by 24 publications

(19 citation statements)

References 55 publications

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“…The only pharmacologic therapy known to reverse T1D in humans and to provide for increased C-peptide production (alongside of gaining exogenous insulin independence) is a method that is commonly termed the "Brazilian protocol" [11][12][13][14][15][16][17]. This method utilized a combination therapy of antithymocyte globulin (ATG), granulocyte colonystimulating factor (G-CSF), cytoxan, and autologous stem cell infusion; it has reported remarkably promising results.…”

Section: Abbreviationsmentioning

confidence: 99%

Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

Driver¹,

Chen²,

Mathews³

2012

Rev Diabet Stud

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Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

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Section: Abbreviationsmentioning

confidence: 99%

Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

Driver¹,

Chen²,

Mathews³

2012

Rev Diabet Stud

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“…The great majority of studies of cell precursors were developed in animal models and each protocol has its own pros and cons (21,22 and then migrated to the pancreatic tissue. Another hypothesis is that pancreatic duct cells differentiate into pancreatic β-cells and it was widely studied in animal models (27).…”

Section: Insights About β-Cell Regenerationmentioning

confidence: 99%

Potencial role of stem cell therapy in type 1 diabetes mellitus

Couri

Voltarelli

2008

Arq Bras Endocrinol Metab

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type 1 diabetes mellitus is the result of the autoimmune response against pancreatic β-cell(s). At the time of clinical diagnosis near 70% of β-cell mass is been destroyed as a consequence of the auto-destruction that begins months or even years before the clinical diagnosis. Although marked reduction of chronic complications was seen after development and progression of insulin therapy over the years for type 1 diabetic population, associated risks of chronic end-organ damage and hypoglycemia still remain. Besides tight glucose control, β-cell mass preservation and/or increase are known to be other important targets in management of type 1 diabetes as long as it reduces chronic microvascular complications in the eyes, kidneys and nerves. Moreover, the larger the β-cell mass, the lower the incidence of hypoglycemic events. in this article, we discuss some insights about β-cell regeneration, the importance of regulation of the autoimmune process and what is being employed in human type 1 diabetes in regard to stem cell repertoire to promote regeneration and/or preservation of β-cell mass. RESuMOO potencial das células-tronco no tratamento do Diabetes Melito tipo 1. o diabetes melito tipo 1 (dM1) é o resultado de uma resposta auto-imune contra as células-beta pancreáticas. Por ocasião do diagnóstico clínico do dM1, aproximadamente 70% da massa de células-beta foram destruídas como conseqüência de uma autodestruição que se iniciou há anos ou meses antes dos primeiros sinais da doença. embora a redução acentuada das complicações crônicas na população com dM1 foi observada após o desenvolvimento e evolução da insulinoterapia, os riscos associados às lesões dos órgãos-alvo e hipoglicemia persistem. Além do controle intensivo da glicemia, a preservação e/ou o aumento da massa de células-beta são reconhecidos como alvos importantes no tratamento do dM1. isto vem associado à redução das complicações crônicas microvasculares na retina, rins e nervos e a menor incidência de eventos hipoglicêmicos. neste artigo, discutimos alguns aspectos da regeneração das células-beta pancreáticas, a importância da regulação do processo auto-imune e o que está sendo empregado no dM1 humano com relação ao repertório das células-tronco nesse sentido.

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“…Techniques that promise to facilitate the use of BMT are currently being studied, including the development of partial conditioning strategies, BM graft engineering to enrich HSCs and cell populations that facilitate engraftment and approaches to limit graft-versushost disease. The use of various stem cell types as sources for ß-cell regeneration is also important, as recently reviewed (49). The end result will be safer BMT, thereby allowing its use in nonmalignant settings such as AD and tolerance induction in solid organ and cell transplantation (48).…”

Section: Diabetes Mellitusmentioning

confidence: 99%