Molecular Medicine

, Volume 21, Issue 1, pp 702–708 | Cite as

Galantamine Attenuates Type 1 Diabetes and Inhibits Anti-Insulin Antibodies in Nonobese Diabetic Mice

  • William M. Hanes
  • Peder S. Olofsson
  • Kevin Kwan
  • LaQueta K. Hudson
  • Sangeeta S. Chavan
  • Valentin A. Pavlov
  • Kevin J. Tracey
Research Article


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 challenge ex 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.



This work was supported by a grant from the Juvenile Diabetes Research Fund and the following grants from the National Institute of General Medical Sciences, National Institutes of Health: R01GM057226 (to KJ Tracey) and R01GM089807 (to KJ Tracey and VA Pavlov).

Supplementary material

10020_2015_2101702_MOESM1_ESM.pdf (407 kb)
Supplementary material, approximately 406 KB.


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Authors and Affiliations

  • William M. Hanes
    • 1
    • 2
  • Peder S. Olofsson
    • 1
  • Kevin Kwan
    • 1
  • LaQueta K. Hudson
    • 1
  • Sangeeta S. Chavan
    • 1
  • Valentin A. Pavlov
    • 1
  • Kevin J. Tracey
    • 1
  1. 1.Laboratory of Biomedical ScienceThe Feinstein Institute for Medical ResearchManhassetUSA
  2. 2.Department of Biochemistry and Cell BiologyStony Brook UniversityStony BrookUSA

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