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Title: Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of {beta} cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a {mu}-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of {beta} cells was attenuated by methadone treatment. It seems that methadone as an opioid agonistmore » may have a protective effect against destruction of {beta} cells and insulitis in the MLDS model of type 1 diabetes.« less
Authors:
;  [1] ;  [2] ;  [3] ;  [4]
  1. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)
  2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)
  3. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)
  4. Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of), E-mail: ghazikha@sina.tums.ac.ir
Publication Date:
OSTI Identifier:
21144127
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 232; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2008.06.020; PII: S0041-008X(08)00285-8; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; GLUCOSE; HYPERGLYCEMIA; INFLAMMATION; INSULIN; INTERFERON; MICE; PANCREAS; RECEPTORS; SECRETION; STREPTOZOCIN