Age- and diabetes-associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ mice.

The diabetes-associated changes in regional brain norepinephrine (NE) concentrations and related adrenergic receptor types were correlated with changes in blood glucose levels and body weight (obesity) in 4-16-week-old C57BL/KsJ (db/db) mice relative to corresponding age-matched control (+/?) parameters. Regional brain (i.e. frontal cortex, septal area, amygdala, hypothalamus and medulla) NE levels were determined by high performance liquid chromatography and compared to the associated changes in tissue alpha-1,2 and beta-adrenergic membrane receptor populations. All db/db mice exhibited overt hyperglycemia and obesity relative to controls between 4 and 16 weeks of age. Regional brain NE levels in diabetics were chronically elevated as compared to those of age-matched controls. All of the alpha 1 and alpha 2 adrenergic receptor populations were elevated in the regional brain samples of diabetics relative to controls. In contrast, beta-adrenergic receptor populations were depressed in diabetics as compared with age-matched controls. These data demonstrate that a marked modification in regional brain adrenergic parameters occurs in association with the overt expression of the diabetes mutation in this species. The observed changes in adrenergic influences in specific CNS loci may be causally related to the recognized diabetes-associated alterations in regional brain structure, function and metabolism in C57BL/KsJ (db/db) mice.