Aminoguanidine, an inhibitor of nitric oxide formation, fails to protect against insulitis and hyperglycemia induced by multiple low dose streptozotocin injections in mice.

Abstract:

:It has been suggested that pancreatic beta-cell destruction occurring during the process leading to insulin-dependent diabetes mellitus (IDDM) involves formation of nitric oxide (NO). We have presently studied the effect of aminoguanidine (AG), which has recently been reported to inhibit generation of NO induced by the cytokine interleukin-1 beta. AG currently counteracted IL-1 beta induced impairment of the glucose oxidation rate in rat pancreatic islets. Then we studied the effect of AG on the development of hyperglycemia and pancreatic insulitis in mice treated with multiple low dose injections of streptozotocin (40 mg/kg body-weight for five consecutive days). It was found that one daily intraperitoneal injection of AG (50 mg/kg body-weight) for 14 days failed to prevent the development of diabetes as well as insulitis following the streptozotocin injections. Furthermore, the mice treated with streptozotocin plus AG showed an increased mortality compared to mice treated with streptozotocin plus saline. Although the present data do not exclude a role for NO in IDDM, it raises concerns about the use of testing AG as therapeutic agent in IDDM.

journal_name

Autoimmunity

journal_title

Autoimmunity

authors

Holstad M,Sandler S

doi

10.3109/08916939309115754

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

311-4

issue

4

eissn

0891-6934

issn

1607-842X

journal_volume

15

pub_type

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