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Insulitis and mechanisms of disease resistance: Studies in an animal model of insulin dependent diabetes mellitus

Insulitis and mechanisms of disease resistance: Studies in an animal model of insulin dependent diabetes mellitus

Journal of Molecular Medicine 77(1): 57-61

Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease characterised by extreme insulin deficiency due to an overall decrease in the mass of properly functioning beta-cells. This reduction occurs as a result of insulitis. the outcome of which will depend upon the intensity of the cytotoxic attack and the ability of beta-cells to resist and repair immune mediated cell damage. To further elucidate the relationship between the insulitis process and beta-cell defence and repair mechanisms in the prevention of diabetes we have studied a unique subgroup of diabetes prone (DP) BB/S rats which have demonstrated an ability to recover from IDDM (BB/S-R). Animals were diagnosed as diabetic at 115 days of age, subsequently receiving insulin therapy (1.49+/-0.1 IU/day) for a total of 19.7 days during 1 to 4 episodes of IDDM. Following a prolonged symptom-free period of 90 days, an IPGTT revealed that BB/S-R rats possessed normal glycaemic control. Islets were isolated from the BB/S-R rats and their glucose-stimulated insulin response was shown to be comparable to Wistar control islets. Furthermore, control and BB/S-R islets showed both a similar structural integrity and insulin content. BB/S-R islets cultured for 24 hr in IL-1beta (10(-13) M) maintained a significant insulin secretory response to glucose in contrast to Wistar controls in which the response was completely inhibited. Nitrite production was induced by IL-1beta, in a dose-dependent manner, in control islets whereas there was no significant increase in production in the islets of BB/S-R rats. These findings suggest that previous immune directed beta-cell attack may induce a state of increased resistance to subsequent deleterious effects of cytokine-mediated cytotoxicity. Overall therefore, the present study shows how the "recovered" BB/S-R rat model provides a unique opportunity to assess the direct effects of insulitis on pancreatic islets and how this interaction may subsequently determine disease outcome.

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Accession: 010858244

Download citation: RISBibTeXText

PMID: 9930928

DOI: 10.1007/s001090050301

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