Reproductive tract and pancreatic norepinephrine levels in pre- and overt-diabetic C57BL/KsJ mice: relationship to body weight, blood glucose, serum insulin, and reproductive dysfunction.

Diabetes-associated changes in tissue norepinephrine (NE) levels were determined in pre- and overt-diabetic C57BL/KsJ (db/db) mice relative to age-matched controls (+/?). At 4 weeks of age, both pre- and overt-diabetic mice exhibited obesity and hyperinsulinemia relative to controls. Prediabetic mice demonstrated normoglycemia and tissue (i.e., pancreatic, ovarian, and uterine) NE levels which were comparable to control levels. However, the hyperglycemic condition that characterized the overt-diabetic mice was found to be associated with significant elevations in tissue NE levels relative to both control and prediabetic values. These data demonstrate that the Type II diabetes-obesity syndrome in this mutant murine model is accompanied by a dramatic imbalance in the adrenergic influence on reproductive tissue glucose homeostasis. The hyperglycemic component of the diabetes-obesity syndrome is temporally linked to the noradrenergic disturbances in this model, which occur independently of insulin- or obesity-related changes that also accompany the expression of the genomic mutation and reproductive tract involution.