Immunological and Metabolic Effects of Prophylactic Insulin Therapy in the NOD-<i>scid/scid</i> Adoptive Transfer Model of IDDM

Bowman, Mark A.; Campbell, Lalita; Darrow, Bethany L.; Ellis, T. M.; Suresh, A.; Atkinson, Mark A.

doi:10.2337/diab.45.2.205

Cited by 42 publications

(21 citation statements)

References 2 publications

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“…One possibility is a protective effect of insulin, whether by allowing exhausted beta cells to rest or by altering the makeup of the T cells in the pancreas destroying the β cells there. The first reason was the basis for the large North American trial in pre-diabetic people in the late 90's with small doses of parenteral insulin [22]. The second reason was the basis for the large North American trial in pre-diabetic people in the very late 90's with oral insulin [23].…”

Section: Discussionmentioning

confidence: 99%

Insulin expressing hepatocytes not destroyed in transgenic NOD mice

et al. 2004

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Background: The liver has been suggested as a suitable target organ for gene therapy of Type 1 diabetes. However, the fundamental issue whether insulin-secreting hepatocytes in vivo will be destroyed by the autoimmune processes that kill pancreatic β cells has not been fully addressed. It is possible that the insulin secreting liver cells will be destroyed by the immune system because hepatocytes express major histocompatibility complex (MHC) class I molecules and exhibit constitutive Fas expression; moreover the liver has antigen presenting activity. Together with previous reports that proinsulin is a possible autoantigen in the development of Type 1 diabetes, the autoimmune destruction of insulin producing liver cells is a distinct possibility.

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Section: Discussionmentioning

confidence: 99%

Insulin expressing hepatocytes not destroyed in transgenic NOD mice

et al. 2004

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“…In previous studies, parenteral insulin therapy was reported that it can prevent diabetes in animal models [7,8], and pilot studies have suggested that insulin therapy also delays diabetes in humans [9,10]. In recently, insulin pump is a safe and effective therapy method in treating children and adolescents with T1D [11], and the sensoraugmented pump therapy could improve the glycated hemoglobin level comparing with injection therapy [12].…”

Section: Bioinformatics Analysis Of Gene Expression In Peripheral Blomentioning

confidence: 99%

Bioinformatics Analysis of Gene Expression in Peripheral Blood Mononuclear Cells from Children with Type 1 Diabetes in 3 Periods

Liu

Sun

et al. 2014

Exp Clin Endocrinol Diabetes

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To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D).Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4).HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.

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“…By comparison, the original study in BB rats used 15 U insulin/kg body weight (53). Actually, the very low human dose was later found not to work, either in BB rats or in NOD mice (56). The human dose used might give an immunological effect, which then was not enough for T1D prevention.…”

Section: The Activity Of the Beta Cellsmentioning

confidence: 99%

Type-specific human papillomavirus detection in cervical smears in Romania

Anton

Peltecu

Socolov³

et al. 2010

Apmis

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To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics. Gluten-free diet is difficult to implement, and short-term intake has no effect. Regarding the onset of the T1D disease process, slow-acting enterovirus and gliadin deposits are speculated to be etiological in genetically susceptible individuals, followed by the mentioned four pathogenetic factors acting in concert. Neutralization of any one of these factors is capable of stopping T1D development, as lessons are learned from the animal models.

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Immunological and Metabolic Effects of Prophylactic Insulin Therapy in the NOD-scid/scid Adoptive Transfer Model of IDDM

Cited by 42 publications

References 2 publications

Insulin expressing hepatocytes not destroyed in transgenic NOD mice

Insulin expressing hepatocytes not destroyed in transgenic NOD mice

Bioinformatics Analysis of Gene Expression in Peripheral Blood Mononuclear Cells from Children with Type 1 Diabetes in 3 Periods

Type-specific human papillomavirus detection in cervical smears in Romania

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