Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction
of β 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 μ-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)-1β, tumor necrosis factor-α and interferon-γ] and increased anti-inflammatory Th2
cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of β cells
was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a
protective effect against destruction of β cells and insulitis in the MLDS model of type 1 diabete
