Concentration-dependent glucose-lowering effects of oral vanadyl are maintained following treatment withdrawal in streptozotocin-diabetic rats.
We have recently reported that treatment with vanadyl sulfate 0.75 mg/mL in drinking water eliminates hyperglycemia in a subset of streptozotocin (STZ)-diabetic rats, with some rats remaining unresponsive to such treatment. In the present study, we demonstrate that unresponsive diabetic animals become normoglycemic when given higher concentrations of vanadyl. Since the subset of rats that require higher concentrations ([HC] 1.25 to 1.50 mg/mL) were found to be more severely diabetic before treatment than those that responded to lower concentrations ([LC] 0.75 to 1.00 mg/mL), the relative amount of residual circulating insulin (LC 36.0 +/- 2.2 v HC 25.6 +/- 3.3 microU/mL) appeared to be a key element in achievement of a normoglycemic effect to a given dose of vanadyl. Similarly, STZ-diabetic animals that responded to euglycemia with a more potent organic vanadyl compound (naglivan) had higher pretreatment plasma insulin levels than unresponsive animals (DT-R) (35.5 +/- 1.9 v 24.2 +/- 3.6 microU/mL). Vanadyl treatment over 10 weeks resulted in a period of normalized glucose levels and glucose tolerance after treatment was stopped. At 20 weeks after withdrawal from treatment with vanadyl sulfate, 13 of 19 animals remained euglycemic, whereas four of seven naglivan-treated animals also maintained normal glucose levels after a 30-week withdrawal period. At 3 weeks after withdrawal, maintenance of normal glucose homeostasis appeared to be independent of altered insulin levels, whereas at 20 weeks an improved insulin secretion, albeit 50% that of age-matched controls both in the fed state and in response to a glucose dose, was sufficient to return plasma glucose levels to the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
Cam
M C
MC
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Faun
J
J
McNeill
J H
JH
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D014638:Vanadates