ar-r-17779 and Diabetes-Mellitus--Type-1

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes.. The alpha-7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR-R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG.. α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein-1 levels were reduced in SG after AR-R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores.. Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Bridged-Ring Compounds; Chemokine CCL2; Diabetes Mellitus, Type 1; Disease Models, Animal; Female; Inflammation; Islets of Langerhans; Mice; Mice, Inbred NOD; Nicotine; Pancreatitis; Saliva; Salivary Glands; Salivation; Sjogren's Syndrome; Spiro Compounds; Tumor Necrosis Factor-alpha; Vagotomy