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Background Recently, the human common salivary protein 1 (CSP1) was identified as an ortholog of the Demilune cell and parotid protein of mouse. However, its function remains to be determined. Here, we show that the serum CSP1 concentration of diabetes mellitus (DM) patients is much higher than that of healthy controls. Methods Recombinant human CSP1 was expressed as a Glutathione-S-transferase (GST)-tagged protein, and the purified fusion protein was used as an immunogen to generate monoclonal antibody (mAb) to CSP1. The produced mAb was tested as a probe in Western blotting of human saliva and in immunohistochemistry of various human tissues. The serum CSP1 levels of 31 DM patients and 38 normal adults were quantified by a house-fabricated CSP1 sandwich enzyme-linked immunosorbent assay (ELISA) system. Results Immunoblot analysis by mAb-hCSP1#4 showed that CSP1 in human saliva exists in a 27 kDa glycosylated form. Among the various human tissues tested, the salivary gland was the only tissue stained with mAb-hCSP1#4 by immunohistochemistry. Quantification of serum CSP1 concentration by CSP1 ELISA showed that the median values (25th–75th percentile) of DM patients and healthy adults were 22.2 (15.8–28.2) and 3.2 (0–11.4), respectively. Student's t-test results indicated that there was a statistically significant difference between the two groups (P

BACKGROUND AND PURPOSE Glucagon-like peptide-1 (GLP-1) receptors are widely expressed in neural tissues and diminish neuronal degeneration or induce neuronal differentiation. The aim of this study was to investigate the effect of the GLP-1 pathway on peripheral nerves in streptozotocin-induced diabetic rats. EXPERIMENTAL APPROACH Diabetic and nondiabetic rats were treated with the GLP-1 receptor agonist, synthetic exendin-4 (i.p., 1 nmol·kg−1·day−1) or placebo for 24 weeks, and current perception threshold values, cAMP levels and nerve fibre size in the sciatic nerve were measured. We also investigated GLP-1 receptor expression, quantitative changes in PGP9.5-positive intraepidermal nerve fibres and cleaved caspase 3–stained Schwann cells by immunohistochemistry. KEY RESULTS GLP-1 receptor expression was detected in the sciatic nerve and skin. After exendin-4 treatment, the increase seen in current perception threshold values at 2000 and 250 Hz in diabetic rats was reduced. Also, the decrease in myelinated fibre size or axon/fibre area ratio in the sciatic nerve and the loss of intraepidermal nerve fibre in the skin of diabetic rats were ameliorated. These responses were closely associated with the attenuation of Schwann cell apoptosis and improvement in the cAMP level in exendin-4-treated diabetic rats, compared with placebo-treated animals. CONCLUSION AND IMPLICATIONS Synthetic exendin-4 may prevent peripheral nerve degeneration induced by diabetes in an animal model, supporting the hypothesis that GLP-1 may be useful in peripheral neuropathy. The neuroprotection is probably attributable to GLP-1 receptor activation, antiapoptotic effects and restoration of cAMP content.

As diabetes mellitus rapidly increases worldwide, diabetic neuropathy is the most common long‐term debilitating complication of diabetes, and is the main initiating factor for foot ulceration and amputation without trauma. Foot ulceration and amputation is much more common in neuropathic patients, with the annual incidence rising from