Hyperglycemic factor in submandibular glands and its etiological relations to diabetes mellitus in mice

Bilateral ligation of both the submandibular and parotid ducts of adult normal and mutant hyperinsulinemic diabetic mice resulted in a significant hypoglycemic effect. Therefore, we postulated that duct ligation may result in the removal of hyperglycemic factor (Hoshino et al., 1976) rather than a change in insulin sensitivity. Indeed, no change in specific binding of 125I-insulin was observed in membrane fractions from several tissues obtained from mice of either sex or strains before and after duct ligation. After slices of the submandibular gland were incubated for 4 hr in Eagle's medium, an aliquot of the culture medium was injected i.p. into normal adult mice. A signigicant hyperglycemic effect was observed in 30 min in the injected animals. Eluates obtained by gel filtration of the crude extract of the submandibular gland were injected into normal adult mice, and hyperglycemia ensued. Thus, it is postulated that ligation of salivary ducts results in glandular atrophy and disappearance of the hyperglycemic factor which in turn leads to hypoglycemia and amelioration of diabetes mellitus, particularly of hyperinsulinemic type.