Publication Date

2015

Journal Title

Mol Med

Abstract

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta 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), interleukin-4 and -6 (IL-4 and IL-6) during KLH-challenge ex vivo. Administration of galantamine beginning at one month of age in non-obese 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.

Volume Number

21

Issue Number

1

Pages

702–708

Document Type

Article

EPub Date

2015/09/01

Status

Faculty; Northwell Researcher; Northwell Resident

Facility

School of Medicine; Northwell Health

Primary Department

Molecular Medicine

Additional Departments

Neurosurgery

PMID

26322849

DOI

10.2119/molmed.2015.00142


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