The functional state of sympathetic nerves in spontaneously diabetic mice.

I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks old) with severe diabetic-like symptoms (blood glucose is greater than 300 mg./100ml.). In the spleen, vas deferens, and adrenal glands of the same animals the NE levels were not changed in relation to control. Other measurements of NE in young (six weeks old) diabetic mice revealed no differences between diabetic and nondiabetic controls. The turnover of NE, a measure of the functional state of sympathetic nerves, decreased significantly in the heart and salivary glands of 24-week-old mice but remained unchanged in the kidney and spleen. In young, diabetic mice the rates of NE turnover in several organs were similar to those found in age-matched controls. The hearts of 24-week-old diabetic mice contained significantly less dopamine-beta-hydroxylase (DBH), an intraneuronal enzyme active in the terminal step of NE biosynthesis. The kidney of the same animals was hypertrophic and showed a massive elevation of monoamine oxidase (MAO), an enzyme that degrades NE to inactive products. Other experiments showed that the regeneration of sympathetic neurons that follows the reversible chemical denervation with 6-hydroxydopamine was comparable in diabetic and nondiabetic animals. It appears that mice with spontaneous diabetes show changes of sympathetic nerve function similar to those noted in diabetic patients with autonomic neuropathy.