Treatment of Type 1 Diabetes by Α7nachr Pathway Activation. (51.11)

Abstract Type 1 diabetes is characterized by autoimmune destruction of insulin-producing pancreatic β cells. The α7 nicotinic acetylcholine receptor (α7nAChR) acts as part of the “cholinergic anti-inflammatory pathway” to inhibit the production of cytokines by monocytes, macrophages, dendritic cells, and other cytokine producing cells. Administration of highly selective α7nAChR agonists in vivo have significantly reversed or prevented the inflammatory damage associated with several preclinical disease models, including collagen induced arthritis, ileus, colitis, ischemia reperfusion injury, sepsis, and autoimmune diabetes. To determine the protective effects of the cholinergic pathway in type 1 diabetes, NOD mice were treated with cholinergic pathway stimulators beginning at an early age (3-4 weeks). Blood glucose was monitored weekly to determine the onset of hyperglycemia, as determined by blood glucose >200 mg/dl. Intervention with cholinergic pathway stimulators at an early age reduced the age of onset of hyperglycemia in NOD mice and reduced the total prevalence of type 1 diabetes. This demonstrates that activation of the α7nAChR may be useful in the early prevention of type 1 diabetes.