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Morphological and carbohydrate histochemical changes were studied in the major salivary glands of male and female mice rendered experimentally diabetic with alloxan. This model presents a hypoinsulinemic, potentially ketotic diabetic syndrome which is non-insulin requiring. Since mouse submandibular gland sexual dimorphism is known to be affected by androgens and diabetes is known to have a hypogonadic effect, the salivary glands of male diabetic mice were compared with unafflicted littermates as well as with diabetic animals supplemented with testosterone or insulin. There was evidence of demasculinization of the submandibular gland in the diabetic male; diameters and granule content of granular ducts were both significantly decreased. Testosterone restored normal morphology. In female diabetics a similar decrease in duct diameters and granules was observed. PAS and PAPS techniques indicated a decrease in neutral- and an increase in sialo-glycoproteins in male diabetic submandibular acini. Testosterone restored normal acinar staining. Granular duct staining, solely neutral in nature, was decreased in diabetic males; neither testosterone nor insulin could restore control levels. Apparently, both testosterone and insulin are required to maintain glycoconjugate content in submandibular granular ducts. Sublingual salivary glands appeared sexually dimorphic due to the prominence of granulated striated ducts in male and testosterone-supplemented mice; diabetic animals had a decreased frequency of these ducts. The carbohydrate histochemistry of sublingual mucous tubules was unaltered by diabetes or testosterone. Neutral glycoconjugate staining of parotid glands was unaffected in the diabetic. However, a dramatic increase in acidic, non-sulfated, glycoproteins was observed with AB staining. Insulin-treated animals had normal AB reactivity, indicating a direct effect of the hypoinsulinemic state on acidic carbohydrate metabolism. It appears that, in the diabetic, a decrease in production of, and/or sensitivity to, androgens must be present, since many of the morphological and histochemical alterations seen in these animals could be at least partially reversed with testosterone. However, our studies indicated that both insulin and testosterone are required for normal carbohydrate metabolism in submandibular glands. Mouse sublingual glands appeared to be unaffected by insulin deficiency while the parotid gland, though androgen insensitive, demonstrated altered carbohydrate metabolism in the insulin-deficient state.