alexa Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid scid adoptive transfer model of IDDM.


Journal of Clinical & Cellular Immunology

Author(s): Bowman MA, Campbell L, Darrow BL, Ellis TM, Suresh A,

Abstract Share this page

Abstract Prophylactic insulin therapy prevents IDDM in spontaneous animal models of the disease and has shown promise in preventing the disease in humans. Although large clinical trials have been formed to use this therapy, a comparative analysis of the efficiency of different pharmaceutical forms and doses of insulin in preventing IDDM has not been performed, and the mechanism underlying the observed prevention of disease is unknown. In the NOD-scid/scid adoptive transfer model of IDDM (10(7) new-onset NOD splenocytes injected intravenously into 6- to 8-week NOD/scid-scid recipients; insulitis develops at 6-9 days post-transfer and 100\% IDDM by 32 days post-transfer), life-table (log-rank) analyses revealed that IDDM can be delayed (compared with insulin-free diluent, once daily, n = 8) with equivalent efficiency by prophylactic administration (-9-50 days post-transfer) of high (metabolism-altering) doses of short-acting (0.5 U, once daily, regular, n = 13) or long-acting (0.5 U, once daily, ultralente, n = 9) insulin as well as non-metabolism-altering low-dose insulin (0.02 U, once daily, regular, n = 8). Furthermore, IDDM was delayed with somatostatin (0.2 microgram, twice daily, n = 11), an agent that suppresses endogenous insulin production. No significant difference was seen between the preventative effects of these agents. In an assessment of when therapies can be initiated and still maintain clinical efficiency, only prophylactic somatostatin therapy delayed IDDM (n = 10, P = 0.02) when initiated at 14 days post-transfer, whereas the short-acting insulin regimen did not retard the onset of IDDM (n = 8, P = 0.25) compared with diluent-treated controls. The 24-h urinary C-peptide levels were significantly reduced with short-acting (-56\%, P = 0.01) and long-acting (-67\%, P = 0.02) insulin products and somatostatin (-59\%, P = 0.02) compared with diluent-treated controls. These results indicate that both immunological and metabolic (i.e., beta-cell rest) factors may contribute to the beneficial effects of prophylactic insulin therapy.
This article was published in Diabetes and referenced in Journal of Clinical & Cellular Immunology

Relevant Expert PPTs

Relevant Speaker PPTs

  • Hedef Dhafir El-Yassin
    The Immune Response of Prolactin and the Induction of Tumor Necrosis Factor (TNF) in Iraqi Patients Infected with Hepatitis C Virus
    PPT Version | PDF Version
  • Ildiko Molnar
    The role of tissue-specific type 2 5’-deiodinase enzyme activities in Graves’ orbitopathy and systemic sclerosis: a new candidate in thyroid autoimmunity
    PDF Version
  • Moshe Giladi
    Tumor Treating Fields (TTFields) induced cancer cell death may be immunogenic resulting in enhanced antitumor efficacy when combined with immune-modulating therapy
    PPT Version | PDF Version
  • M Shahnawaz Khan
    Graphene Oxide @ Gold Nanorods Conjugate for Controlled Release of Doxorubicin in tumor
    PPT Version | PDF Version
  • Ming-Yow Hung
    Innate immunity in cardiology: Vessel and valve
    PPT Version | PDF Version
  • Omar E Franco
    Heterogeneous Tumor Stroma and Prostate Carcinogenesis
    PPT Version | PDF Version
  • Yen-Chein Lai
    Molecular pathogenesis in granulosa cell tumor is not only due to somatic FOXL2 mutation
    PPT Version | PDF Version
  • Babak Behnam
    SLUG and SOX9 Cooperatively Regulate Tumor Initiating Niche Factors in Breast Cancer
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Fan-Gang Tseng
    PPT Version | PDF Version
  • Myron R Szewczuk
    Therapeutic targeting neuraminidase-1 in multi-stage of tumorigenesis
    PPT Version | PDF Version
  • Hawa ZE Jaafar
    Involvement of elicitated Labisia pumila Benth. biofluids in the alleviation of chemotoxicity effect and antitumor activity
    PPT Version | PDF Version
  • Huidi Liu
    Reduced Expression of SOX7 in Ovarian Cancer: a Novel Tumor Suppressor through the Wnt/β-catenin Signaling Pathway
    PPT Version | PDF Version
  • Alex Soltermann
    Lung neuroendocrine tumors: Correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN
    PPT Version | PDF Version
  • Fu Shi Quan
    Influenza virus-like particle vaccines elicit protective immunity in the early stage of vaccination
    PPT Version | PDF Version

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version