title: Galantamine Attenuates Type 1 Diabetes and Inhibits Anti-Insulin Antibodies in Nonobese Diabetic Mice.
abstract: Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic β-cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B-cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin (KLH) significantly suppressed splenocyte release of immunoglobulin G (IgG) and interleukin (IL)-4 and IL-6 during KLH challengeex vivo. Administration of galantamine beginning at 1 month of age in nonobese diabetic (NOD) mice significantly delayed the onset of hyperglycemia, attenuated immune cell infiltration in pancreatic islets and decreased anti-insulin antibodies in serum. These observations indicate that galantamine attenuates experimental type 1 diabetes in mice and suggest that activation of the inflammatory reflex should be further studied as a potential therapeutic approach.
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.
authors: William M
authors: WM
authors: Hanes
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: Peder S
authors: PS
authors: Olofsson
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: Kevin
authors: K
authors: Kwan
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: LaQueta K
authors: LK
authors: Hudson
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: Sangeeta S
authors: SS
authors: Chavan
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: Valentin A
authors: VA
authors: Pavlov
authors: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors: Kevin J
authors: KJ
authors: Tracey