Previous observations have suggested that the salivary glands exercise a regulatory role on insulin secretion and/or glucose metabolism. We have challenged the issue by studying in unanesthetized, unrestrained rats the short- and long-term effect of selective sialoadenectomy on the animals' ability to meet an intra-arterial glucose challenge. Ten-minute intra-arterial glucose tolerance tests were carried out in chronically catheterized adult rats before and after sialoadenectomy. Eighty-five to 100 days postsurgery, the parotidectomized rats experienced a 45% reduction in plasma immunoreactive insulin output (P < .001) compared with the sham-operated animals; the plasma glucose levels of the test subjects remained 19% higher (P < .001) than those of the control group. In younger rats, similar observations were made; however, the difference in insulin and glucose responses between treatments was less than in the adult rats. Our findings suggest that the insulinotropic effect resides primarily with the parotids, and the role of the submandibular glands seems to be permissive at best. We hypothesize that parotidectomy deprives the β-cells of a humoral principle that appears to be essential for optimizing the immediate insulin response to a glucose challenge. These results suggest that the insulinotropic effect of the parotids is of particular importance when aging changes insulin secretion and action.

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