RT Journal Article
SR Electronic
T1 Nicotine Reduces the Incidence of Type I Diabetes in Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 876
OP 881
DO 10.1124/jpet.300.3.876
VO 300
IS 3
A1 J. G. Mabley
A1 P. Pacher
A1 G. J. Southan
A1 A. L. Salzman
A1 C. Szabó
YR 2002
UL http://jpet.aspetjournals.org/content/300/3/876.abstract
AB Nicotine has been previously shown to have immunosuppressive actions. Type I diabetes is an autoimmune disease resulting from the specific destruction of the insulin-producing pancreatic β-cells. Thus, we hypothesized that nicotine may exert protective effects against type I diabetes. The multiple low-dose streptozotocin (MLDS)-induced model and spontaneous nonobese diabetic (NOD) mouse model of type I diabetes were used to assess whether nicotine could prevent this autoimmune disease. Blood glucose levels, diabetes incidence, pancreas insulin content, and cytokine levels were measured in both models of diabetes, both to asses the level of protection exerted by nicotine and to further investigate its mechanism of action. Nicotine treatment reduced the hyperglycemia and incidence of disease in both the MLDS and NOD mouse models of diabetes. Nicotine also protected against the diabetes-induced decrease in pancreatic insulin content observed in both animal models. The pancreatic levels of the Th1 cytokines interleukin (IL)-12, IL-1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased in both MLDS-induced and spontaneous NOD diabetes, an effect prevented by nicotine treatment. Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2. The American Society for Pharmacology and Experimental Therapeutics