| Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid/scid adoptive transfer model of IDDM. | |
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MedLine Citation:
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PMID: 8549866 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M A Bowman; L Campbell; B L Darrow; T M Ellis; A Suresh; M A Atkinson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Diabetes Volume: 45 ISSN: 0012-1797 ISO Abbreviation: Diabetes Publication Date: 1996 Feb |
Date Detail:
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Created Date: 1996-02-21 Completed Date: 1996-02-21 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 205-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32610-0275, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals C-Peptide / metabolism Diabetes Mellitus, Type 1 / immunology, metabolism, prevention & control* Immunization, Passive Insulin / administration & dosage* Mice Mice, Inbred NOD Mice, SCID Somatostatin / therapeutic use Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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R29-DK-45342/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/C-Peptide; 11061-68-0/Insulin; 51110-01-1/Somatostatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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