Immunobiology of β-cell destruction

Lund University, Clinical Research Center (CRC), Department of Clinical Sciences, Malmö, Sweden.
Advances in Experimental Medicine and Biology (Impact Factor: 1.96). 01/2012; 771:194-218.
Source: PubMed


Type 1 diabetes is a chronic disease characterized by severe insulin deficiency and hyperglycemia, due to autoimmune destruction of pancreatic islets of Langerhans. A susceptible genetic background is necessary, but not sufficient, for the development of the disease. Epidemiological and clinical observations underscore the importance of environmental factors as triggers of type 1 diabetes, currently under investigation. Islet-specific autoantibodies precede clinical onset by months to years and are established tools for risk prediction, yet minor players in the pathogenesis of the disease. Many efforts have been made to elucidate disease-relevant defects in the key immune effectors of islet destruction, from the early failure of specific tolerance to the vicious circle of destructive insulitis. However, the events triggering islet autoimmunity as well as the transition to overt diabetes are still largely unknown, making prevention and treatment strategies still a challenge.

4 Reads
  • Source
    • "Type 1 diabetes mellitus is a disease of insulin insufficiency that results from the autoimmune destruction of pancreatic β-cell in vivo [1]. It is a lifelong disorder depending on exogenous insulin replacement and prone to acquire serious acute and chronic complications [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research design and methods: Streptozotocin (65 mg·kg⁻¹) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-²H₂] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-¹⁴C]-2-deoxy-glucose. Results: Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions: The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo.
    Full-text · Article · Mar 2014 · Journal of Diabetes Research
  • Source
    • "Type 1 diabetes mellitus is a chronic metabolic organ-specific progressive disease in which pancreatic insulin-secreting beta-cells are destroyed by immune-mediated mechanisms, resulting in detrimental effects on all parts of the body, inducing degenerative complications in various organs, particularly the insulin-secreting pancreatic cells (Knip et al., 2011; Lernmark and Larsson, 2013; Vaarala, 2012). None of the potential primary determinants of the initiation of the pancreatic beta-cell autoimmune process in type 1 diabetes has been unequivocally established (Knip et al., 2011; Lernmark and Larsson, 2013; Vaarala, 2012; La Torre, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to examine the possible binding of bovine insulin (BI) with bovine serum albumin (BSA) to form a new potential diabetogenic irreversible complex protein. Several preparations of BSA and BI were prepared. Both capillary electrophoresis and spectrophotometric analysis were undertaken to test the possibility of complexation between BI and BSA. HPLC was used to test whether the potential complex of BI and BSA is reversible or irreversible. The optimum deviation between the real and calculated absorbances was observed at a BI/BSA ratio of 2. Moreover, the migration time of BI decreased substantially with increasing ratio of BI to BSA until it became almost constant at equal molar ratio of BI/BSA. While the majority of the 2:1 BI-BSA sample detached during the HPLC analysis, which confirms the reversible character of BI-BSA binding, the HPLC chromatogram also emphasizes the formation of an irreversible complexation between the two proteins. This study provides evidence of the formation of reversible and irreversible new BI-BSA complexes under physiological conditions. This highlights the importance of examining the possible diabetogenicity of BI-BSA complex in genetically susceptible people. Copyright © 2013 John Wiley & Sons, Ltd.
    Full-text · Article · Mar 2014 · Biomedical Chromatography
  • Source
    • "Another interesting finding was also reported by Maier et al. of a lack of an association of IL-4 and IL-13 polymorphisms with type 1 diabetes mellitus (T1DM) in white British population [8]. This finding surely points to the different immunopathology of the two diseases particularly noting that T1DM is an autoimmune disease with an underlying mechanism which is different from the immune modulation and insulin resistance impacting the presentation of T2DM [20–22]. However, taking into consideration the study limitations, particularly related to its relatively small sample size, we recommend another wider scale study with a higher number of cases and controls to investigate all genetic and probably also protein polymorphisms related to the Th1 and Th2 inflammatory pathways. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The goal of the study is to investigate the association of IL-4-590 and IL-13-1112 genetic polymorphisms with type 2 diabetes mellitus (T2DM) in Egyptian patients. Subjects and methods: The study included 135 cases with T2DM and 75 healthy unrelated age-matched controls from the same locality of Egypt. DNA was extracted and processed by the ARMS-PCR technique for characterization of genetic variants of IL-4-590 C>T and IL-13-1112 C>T polymorphisms. Results: Egyptian cases with T2DM showed a lower frequency of the IL-4-590 CC homozygous genotype compared to controls (10.4% versus 43.48%) with a higher CT heterozygous genotype (85.2% versus 47.8%). Similarly, cases showed a lower frequency of the IL-13-1112 CC genotype (20.7% versus 56.8%) with a higher frequency of the heterozygous IL-13-1112 CT genotype (76.3% versus 41.3%). Both polymorphisms showed significantly positive associations with T2DM in the dominant, codominant, and overdominant models of inheritance. On the other hand, comparing genotypes of subgroups related to gender, positive family history, and positive consanguinity showed a nonsignificant difference (P > 0.05). Conclusion: Heterozygous genotypes (IL-4-590 CT and IL-13-1112 CT) could be considered as risk factors, while the homozygous wild types (-590 CC and -1112 CC) might be considered protective to T2DM.
    Full-text · Article · Sep 2013 · Disease markers
Show more