scholarly journals 100 years post insulin: immunotherapy as the next frontier in Type 1 Diabetes

2021 ◽  
Author(s):  
James A Pearson ◽  
Eoin F McKinney ◽  
Lucy S K Walker
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Turning Point ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Selection Of ◽  
New Onset

Abstract Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell-mediated destruction of the insulin-producing β cells in the pancreas. Similar to other autoimmune diseases, the incidence of T1D is increasing globally. The discovery of insulin 100 years ago dramatically changed the outlook for people with T1D, preventing this from being a fatal condition. As we celebrate the centenary of this milestone, therapeutic options for T1D are once more at a turning point. Years of effort directed at developing immunotherapies are finally starting to pay off, with signs of progress in new onset and even preventative settings. Here we review a selection of immunotherapies that have shown promise in preserving β cell function and highlight future considerations for immunotherapy in the T1D setting.

β-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial

The Lancet ◽  
2001 ◽  
Vol 358 (9295) ◽  
pp. 1749-1753 ◽  
Author(s):  
Itamar Raz ◽  
Dana Elias ◽  
Ann Avron ◽  
Merana Tamir ◽  
Muriel Metzger ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Function ◽  
Phase Ii Trial ◽  
Β Cell ◽  
Double Blind ◽  
Β Cell Function ◽  
New Onset

Can Functionally Mature Islet β-Cells Be Derived from Pluripotent Stem Cells? – A Step Towards Ready-To-Use β-Cells in Type 1 Diabetes

2020 ◽  
Vol 15 ◽  
Author(s):  
Bishnu K Khand ◽  
Ramesh R Bhonde
Keyword(s):  
Stem Cells ◽  
Type 1 Diabetes ◽  
Pluripotent Stem Cells ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

: Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer’s disease. PSC-derived pancreatic islet β-cells appear to be as a promising therapy for type 1 diabetes patients with impaired β-cell function. Several protocols have been developed to derive β-cells from PSCs. However, these protocols produce β-like cells that show low glucose stimulated insulin secretion [GSIS] function and mirror GSIS profile of functionally immature neonatal β-cells. Several studies have documented a positive correlation between the sirtuins [a family of ageing-related proteins] and the GSIS function of adult β-cells. We are of the view that GSIS function of PSC-derived β-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the β-cell development and inclusion of the sirtuin activator and inhibitor cocktail [specific to a developmental stage] in the present protocols may help us derive functionally mature, ready-to-use β-cells in-vitro making them suitable for transplantation in type 1 diabetes.

scholarly journals A20 Inhibits β-Cell Apoptosis by Multiple Mechanisms and Predicts Residual β-Cell Function in Type 1 Diabetes

2016 ◽  
Vol 30 (1) ◽  
pp. 48-61 ◽  
Author(s):  
Makiko Fukaya ◽  
Caroline A. Brorsson ◽  
Kira Meyerovich ◽  
Leen Catrysse ◽  
Diane Delaroche ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Type 1 Diabetes ◽  
Cell Function ◽  
Nucleotide Polymorphism ◽  
Β Cells ◽  
Β Cell ◽  
Single Nucleotide ◽  
Β Cell Function ◽  
Diabetes Outcome

Abstract Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to β-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-κB signaling and has strong antiapoptotic activities in β-cells. Although the role of A20 on NF-κB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the β-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in β-cells that are not restricted to inhibition of NF-κB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual β-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of β-cell survival and unveil novel mechanisms by which A20 controls β-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.

scholarly journals Preventing type 1 diabetes in childhood

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. 506-510 ◽  
Author(s):  
Colin M. Dayan ◽  
Rachel E. J. Besser ◽  
Richard A. Oram ◽  
William Hagopian ◽  
Manu Vatish ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Large Scale ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Genetic Risk Assessment ◽  
Recent Success ◽  
Β Cell Function ◽  
Cell Preservation

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing β cells of the pancreas are destroyed by T lymphocytes. Recent studies have demonstrated that monitoring for pancreatic islet autoantibodies, combined with genetic risk assessment, can identify most children who will develop T1D when they still have sufficient β cell function to control glucose concentrations without the need for insulin. In addition, there has been recent success in secondary prevention using immunotherapy to delay the progression of preclinical disease, and primary prevention approaches to inhibiting the initiating autoimmune process have entered large-scale clinical trials. By changing the focus of T1D management from late diagnosis and insulin replacement to early diagnosis and β cell preservation, we can anticipate a future without the need for daily insulin injections for children with T1D.

scholarly journals Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1cin New-Onset Type 1 Diabetes

Diabetes Care ◽  
2018 ◽  
Vol 41 (9) ◽  
pp. 1917-1925 ◽  
Author(s):  
Michael J. Haller ◽  
Desmond A. Schatz ◽  
Jay S. Skyler ◽  
Jeffrey P. Krischer ◽  
Brian N. Bundy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Low Dose ◽  
Cell Function ◽  
Β Cell ◽  
Onset Type ◽  
Β Cell Function ◽  
New Onset

scholarly journals Updates on Immune Therapies in Type 1 Diabetes

2016 ◽  
Vol 12 (2) ◽  
pp. 89 ◽  
Author(s):  
Bimota Nambam ◽  
◽  
Michael J Haller ◽  
Keyword(s):  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Cell Function ◽  
Β Cell ◽  
Immune Therapies ◽  
Β Cell Function ◽  
Potential Benefits ◽  
New Onset

Multiple clinical trials investigating the efficacy and safety of immunotherapeutic interventions in new onset type 1 diabetes (T1D) have failed to yield long term clinical benefit. Lack of efficacy has frequently been attributed to an incomplete understanding of the pathways involved in T1D and the use of single immunotherapeutic agents. Recent mechanistic studies have improved our knowledge of the complex etiopathogenesis of T1D. This in turn has provided the framework for new and ongoing clinical trials in new onset T1D patients and at-risk subjects. Focus has also shifted towards the potential benefits of synergistic combinatorial approaches, both in terms of efficacy and the potential for reduced side effects. These efforts seek to develop intervention strategies that will preserve β-cell function, and ultimately prevent and reverse clinical disease.

Association of T-cell reactivity with β-cell function in recent onset type 1 diabetes patients

2010 ◽  
Vol 34 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Christian Pfleger ◽  
Guido Meierhoff ◽  
Hubert Kolb ◽  
Nanette C. Schloot
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Function ◽  
Β Cell ◽  
Cell Reactivity ◽  
Recent Onset ◽  
Onset Type ◽  
Β Cell Function ◽  
T Cell Reactivity
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