Detection of Alterations in the Levels of Neuropeptides and Salivary Gland Responses in the Non‐Obese Diabetic Mouse Model for Autoimmune Sialoadenitis

The salivary glands of non‐obese diabetic (NOD) mice and BALB/c controls were evaluated for the stimulatory effects of the following neuropeptides; substance P (SP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY). Injection of either of the three neuropeptides in combination with the muscarinic–cholinergic agonist pilocarpine increased saliva flow rates in BALB/c mice while there was no observable augmentation to flow rates in pre‐diabetic or diabetic NOD mice. Small increases in protein content of the stimulated saliva were observed in the BALB/c group of animals with the injection of any of the above neuropeptides in combination with pilocarpine. In pre‐diabetic NOD animals, only VIP and NPY increased the protein content‐ratio above pilocarpine alone. Radioimmunoassay determination of neuropeptide concentrations in the submandibular and parotid glands revealed reduced levels of SP with diabetes onset as compared with pre‐diabetic NOD or BALB/c mice. The levels of NPY were similar between BALB/c and NOD animals except in the pre‐diabetic parotid gland where NPY concentrations were 1.3‐fold greater. On the other hand, VIP concentrations were substantially reduced in the submandibular gland of NOD mice, while in the parotid gland neuropeptide levels were evaluated 3.8‐fold relative to BALB/c controls. Immunohistochemical staining of the parotid and submandibular glands for SP revealed primarily ductal cell staining which was reduced with diabetes onset in NOD animals. These findings further define the sialoadenitis observed in NOD mice to be due, in part, to a general loss of neurotransmitter responsiveness on the part of salivary gland cells.