Characterization of increased plasma dopamine-beta-hydroxylase activity in rats with experimental diabetes.
Plasma dopamine-beta-hydroxylase (pDBH) activity is markedly elevated in chronic experimental streptozotocin (STZ) diabetes in the rat. Several possible explanations, all potentially relevant to the pathophysiology of diabetes, could explain this observation. The objective of this paper was to further delineate the behavior of pDBH in diabetes and examine several possible mechanisms fot the increase. Plasma DBH increases within 1 day of STZ administration, is fivefold elevated within 1 wk, and slowly reaches ninefold control values after several months. Similar changes result from alloxan-induced diabetes. The increase in pDBH activity correlates well with the severity of diabetes as assessed by plasma glucose levels. Reversal of the diabetic state with insulin administration or islet cell transplantation results in the decrease of pDBH activity toward normal values. Plasma DBH is not increased in hyperglycemic obese (ob/ob) mice, suggesting a primary dependence of pDBH elevation on reduced levels of insulin and not hyperglycemia per se. Guanethidine-sympathectomized and sympathectomized/adrenal demedullated animals, with 60% and 25% of control levels of pDBH, respectively, show the same percentage increase in pDBH activity with induction of diabetes, thus, the increase in pDBH does not result from a selective activation or dysfunction of the sympathetic nervous system or adrenal medulla in diabetic animals. No evidence is found for the alteration of the kinetic parameters, molecular size, or charge of pDBH in diabetes. Several mechanisms for the increase are considered.
D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004299:Dopamine beta-Hydroxylase / Q000097:blood*; D005728:Ganglia, Sympathetic / Q000502:physiology; D006145:Guanethidine / Q000494:pharmacology; D007328:Insulin / Q000627:therapeutic use; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000201:enzymology; D010673:Pheochromocytoma / Q000201:enzymology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D004299:Dopamine beta-Hydroxylase; D006145:Guanethidine