New and future immunomodulatory therapy in type 1 diabetes

Tooley, James E.; Waldron‐Lynch, Frank; Herold, Kevan C.

doi:10.1016/j.molmed.2012.01.001

Cited by 38 publications

(25 citation statements)

References 77 publications

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“…Although improvement was transient, this therapy holds promise for those at risk of T1D if administered earlier in the disease process. Genetic screening and earlier diagnosis will be important for opening an earlier therapeutic window of intervention [175,176].…”

Section: Discussionmentioning

confidence: 99%

Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse

2013

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T1D (Type 1 diabetes) is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Studies in T1D patients have been limited by the availability of pancreatic samples, a protracted pre-diabetic phase and limitations in markers that reflect β-cell mass and function. The NOD (non-obese diabetic) mouse is currently the best available animal model of T1D, since it develops disease spontaneously and shares many genetic and immunopathogenic features with human T1D. Consequently, the NOD mouse has been extensively studied and has made a tremendous contribution to our understanding of human T1D. The present review summarizes the key lessons from NOD mouse studies concerning the genetic susceptibility, aetiology and immunopathogenic mechanisms that contribute to autoimmune destruction of β-cells. Finally, we summarize the potential and limitations of immunotherapeutic strategies, successful in NOD mice, now being trialled in T1D patients and individuals at risk of developing T1D.

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Section: Discussionmentioning

confidence: 99%

Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse

2013

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“…[11][12] The emerging understanding of correlations between the immune system and the pathogenesis of diabetes brings a new approach in diabetes treatment, named immunomodulatory therapy. 13 Among several immunomodulatory agents tested, interleukin 10 (IL-10) was assessed as a cytokine that could be used in the treatment of diabetes. IL-10 has a protective effect in type 1 diabetes [14][15] and type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Antihyperglycemic effect of Sesbania grandiflora seed decoction on streptozotocin-induced diabetic mice: Inflammatory status and the role of interleukin-10

Zamroni

Widjanarko

Rifa’i

et al. 2017

AIP Conference Proceedings

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Abstract. Diabetes is one of the fastest growing diseases in the world: its prevalence is estimated to reach 642 million people, or one-tenth of adults will have diabetes by 2040. Traditional herbal exploration and investigation are needed in order to discover medicines that have potential anti-diabetic activity, with no or lower side effects than the medicines clinically used today. In this research, we investigated the anti-hyperglycemic activity of an aqueous decoction of Sesbania grandiflora seeds in streptozotocin-induced diabetic mice, and analyzed the immune responses that occurred during the counter balance process to reach blood glucose homeostasis. Our results revealed that administration of the aqueous decoction (2.5 g/kg BW) could lower the blood glucose levels of diabetic mice from an initial blood glucose level of 435 mg/dl to 213 mg/dl within 18 days of treatment. Analysis of inflammatory markers showed that there was no significant difference in the relative amounts of CD4 + CD62L -, CD8 + CD62L -, TNF-α or IFN-γ between the experimental groups, which revealed that there were no pro-inflammatory responses involved either in hyperglycemia or in the blood glucose lowering process. On the other hand, an increased amount of interleukin-10 in diabetic mice treated with an S. grandiflora seed decoction indicated a role for IL-10 in maintaining blood glucose homeostasis.

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“…Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that afflicts a million persons in the USA [1, 2]. It is a polygenic disorder resulting from the interaction of multiple gene variants [3] and environmental factors [4].…”

Section: Introductionmentioning

confidence: 99%

The Missing Heritability in T1D and Potential New Targets for Prevention

Pierce

Eberwine

Noble³

et al. 2013

Journal of Diabetes Research

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Type 1 diabetes (T1D) is a T cell-mediated disease. It is strongly associated with susceptibility haplotypes within the major histocompatibility complex, but this association accounts for an estimated 50% of susceptibility. Other studies have identified as many as 50 additional susceptibility loci, but the effect of most is very modest (odds ratio (OR) <1.5). What accounts for the “missing heritability” is unknown and is often attributed to environmental factors. Here we review new data on the cognate ligand of MHC molecules, the T cell receptor (TCR). In rats, we found that one allele of a TCR variable gene, Vβ13A, is strongly associated with T1D (OR >5) and that deletion of Vβ13+ T cells prevents diabetes. A role for the TCR is also suspected in NOD mice, but TCR regions have not been associated with human T1D. To investigate this disparity, we tested the hypothesis in silico that previous studies of human T1D genetics were underpowered to detect MHC-contingent TCR susceptibility. We show that stratifying by MHC markedly increases statistical power to detect potential TCR susceptibility alleles. We suggest that the TCR regions are viable candidates for T1D susceptibility genes, could account for “missing heritability,” and could be targets for prevention.

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New and future immunomodulatory therapy in type 1 diabetes

Cited by 38 publications

References 77 publications

Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse

Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse

Antihyperglycemic effect of Sesbania grandiflora seed decoction on streptozotocin-induced diabetic mice: Inflammatory status and the role of interleukin-10

The Missing Heritability in T1D and Potential New Targets for Prevention

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