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)