Characterization of immunoreactive insulin in human saliva: evidence against production in situ.

The presence of insulin immunoreactivity in extra-pancreatic tissues and fluids suggests multiple sites of insulin production. Immunoreactive insulin occurs in human saliva and concentrations increase after oral glucose ingestion. The goal of these experiments was to determine whether the presence of immunoreactive insulin in this extra-pancreatic site is independent of pancreatic production or merely represents the accumulation of circulating pancreatic insulin. The mean +/- SEM concentration of extracted salivary immunoreactive insulin in five normal volunteers increased during an oral glucose tolerance test from basal values of 36 +/- 3.0 to 291 +/- 40 pmol/l; however, the peak occurred 45-90 min later than in serum. On this basis, it was not possible to distinguish between the stimulation (by increased blood glucose concentrations) of insulin synthesis in the saliva glands from the accumulation of blood insulin. Therefore, we studied a group of five volunteers during intravenous infusion of insulin (1 and 10 mU X kg-1 X min-1, sequentially) and glucose (euglycaemic clamp). Under these conditions, salivary immunoreactive insulin concentrations increased significantly from 254 +/- 100 to 1919 +/- 437 pmol/l (p less than 0.05), while simultaneous mean plasma C-peptide concentrations were unchanged. Thus, the concentration of salivary immunoreactive insulin was clearly related to the amount of insulin in the blood and not to the plasma glucose concentration. Physico-chemical and immunological characterization of salivary immunoreactive insulin by dilution in radioimmunoassay, gel filtration and polyacrylamide disc gel electrophoresis demonstrated that the majority of it was indistinguishable from insulin standards.(ABSTRACT TRUNCATED AT 250 WORDS)