Dysfunction of the salivary gland in NOD mouse

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The non-obese diabetic (NOD) mouse has been recognized as an animal model for autoimmune type 1 insulin-dependent diabetes mellitus and has been shown a loss in secretory function of the salivary glands. To understand the salivary functional changes of the salivary gland in NOD mouse, the following investigations were carried out.(1) The secretory response to muscarinic receptor stimulation : NOD showed a reduced potential for the generation of cAMP in the glands. Basal and agonist stimulated concentrations of inositol phosphate were reduced in submandibular gland of NOD mice. The receptor density was decreased in the glands. The reduction of muscarinic agonist response was suggested to be due to a generalized reduction in signal transduction components as a consequence of autoantibodies detected against cell surface antigens.(2) The levels of neuropeptides and salivary gland responses : Injection of either of the three neuropeptides, substance P (SP), vasoactive intestinal polypeptide … More (VIP), and neuropeptide Y (NPY), in combination with the muscarinicchorinergic agonist pilocarpine increased saliva flow rates in Balb/c mice while threr was no observable augmentation to flow rates in NOD mice. Radioimmunoassay determination of neuropeptide concentrations in the submandibular and parotid glands revealed reduced levels of SP with diabetic onset. VIP concentrations were reduced in the submandibular gland of NOD mice. The findings suggested the dysfunction observed in NOD mice to be due to a general loss of neurotransmitter responsiveness on the part of salivary gland cells.(3) Gastrointestinal absorption of Insulin-like growth factor (IGF) and the levels of Insulin-like growth factor binding protein (IGFBP) : IGFBP were detected in the sera, but not in the saliva. Gavage administration of radiolabeled IGF indicated substantial uptake from the gastrointestinal tract and significant tissue distribution. The tissue distribution in the diabetic NOD mouse was reduced, which suggest to contribute to reduced growth and wound healing potentials. Less