An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

Hanifi-Moghaddam, Pejman; Schloot, Nanette C.; Kappler, S.; Seißler, Jochen; Kolb, Hubert

doi:10.2337/diabetes.52.5.1137

Cited by 74 publications

(59 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vivo, the observed decrease in L-cell numbers could be due to direct toxic action of streptozotocin plus accompanying glucose toxicity as there was no evidence of intestinal lymphocyte infiltration. However, our in vitro observations indicate susceptibility of L-cells to cytokines and thus elevated concentrations of pro-inflammatory cytokines and glucose observed in circulation in type 1 diabetes (Lechleitner et al 2000, Hanifi-Moghaddam et al 2003, Chatzigeorgiou et al 2010 could affect L-cell function and survival. Elevated level of TNFa after a single high-dose streptozotocin treatment has been reported recently (Ho et al 2014), but further investigations are required to assess cytokine levels after multiple low-dose streptozotocin treatment.…”

Section: Discussionmentioning

confidence: 72%

Responses of GLP1-secreting L-cells to cytotoxicity resemble pancreatic β-cells but not α-cells

Vasu

Moffett

McClenaghan

et al. 2014

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Little is known about responses of intestinal L-cells to chemical or cytokine-mediated attack and how these compare with pancreatic b-or a-cells. Administration of streptozotocin to mice induced severe diabetes, islet lymphocytic infiltration, increased a-cell proliferation and decreased numbers of b-and L-cells. In vitro, streptozotocin and cytokines reduced cell viability with higher lethal dose 50 values for a-TC1 cells. mRNA expression of Glut2 was lower and Cat was greater in GLUTag and a-TC1 cells compared with MIN6 cells. Cytotoxins affected the transcription of genes involved in secretion in GLUTag and MIN6 cells. They are also involved in upregulation of antioxidant defence enzymes, transcription of NfkB and Nos2, and production of nitrite in all cell types. Cytotoxin-induced DNA damage and apoptosis were apparent in all cells, but a-TC1 cells were less severely affected. Thus, responses of GLP1-secreting L-cells to cytotoxicity resemble b-cells, whereas a-cells are resistant due to differences in the expression of genes involved in cytotoxicity or antioxidant defence.

show abstract

Section: Discussionmentioning

confidence: 72%

Responses of GLP1-secreting L-cells to cytotoxicity resemble pancreatic β-cells but not α-cells

Vasu

Moffett

McClenaghan

et al. 2014

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…Another possibility is the induction of antibody reactivity against GAD and the development of full-blown diabetes, mediated by IL-18 and other proinflammatory cytokines. In particular, IL-18 is presumed to play a pathogenetic role in T1DM, specifically because this cytokine appears to be involved in acceleration of the development of overt disease [152,[158][159][160] . IL-18 can induce both Th1 and Th2 responses, depending on the surrounding cytokines [161] , and this cytokine plays a pathogenic role in several diseases [161] , including acute hepatic injury [162] .…”

Section: Direct Effects Of Hcv and Irmentioning

confidence: 99%

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Antonelli

Ferrari

Giuggioli

et al. 2014

WJD

View full text Add to dashboard Cite

cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients. AbstractHepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory Submit a

show abstract

“…Experimental data from T1D patients and animal models also suggests a role for MIF in T1D development [9][10][11][12]. We have performed the most comprehensive screening of the MIF gene and its surrounding genomic region to date to identify variants and obtain allele frequencies for our population.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus

Martin¹,

Savage²,

Carson

et al. 2010

Diabetic Medicine

View full text Add to dashboard Cite

Aims Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine whose production is transcriptionally regulated by glucose. Experimental data from both Type 1 diabetes mellitus (T1D) patients and animal models suggests a role for MIF in the development of T1D. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the MIF gene and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a combination of case-control and family-based association analyses in order to assess the association of MIF htSNPs with the development of T1D in a white population.Methods All exons, introns and approximately 3 kb upstream and downstream of the MIF gene were screened for DNA polymorphisms in 46 individuals using DNA sequencing. Genotyping of the htSNPs was performed in 432 cases, 407 control subjects and 290 T1D parent-offspring trios, using Taqman, Sequenom, Pyrosequencing and fluorescence-based microsatellite technologies.Results Twenty-three polymorphisms (two novel) with a minor allele frequency > 10% were identified. Four MIF htSNPs (rs875643 G>A, rs7388067 C>T, rs5844572 ) ⁄ CATT, rs6003941 T>G) were identified. Allele and haplotype frequencies were similar between case and control groups (P > 0.6 by permutation test) and assessment of allele transmission distortion from informative parents to affected offspring also failed to find an association. Stratification of these analyses for age-at-onset and human leukocyte antigen (HLA)-DR risk group (DR3 ⁄ DR4) did not reveal any significant associations.Conclusions It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population.

show abstract

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

Cited by 74 publications

References 49 publications

Responses of GLP1-secreting L-cells to cytotoxicity resemble pancreatic β-cells but not α-cells

Responses of GLP1-secreting L-cells to cytotoxicity resemble pancreatic β-cells but not α-cells

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus

Contact Info

Product

Resources

About