Dexamethasone-induced insulin resistance and pancreatic adaptive response in aging rats are not modified by oral vanadyl sulfate treatment.
OBJECTIVE
To explore the adaptive response of the endocrine pancreas in vivo and in vitro and the possible beneficial effect of the insulino-mimetic agent vanadyl sulfate (VOSO(4)), using glucocorticoid treatment to increase insulin resistance, in aging rats.


METHODS
Dexamethasone (Dex) (0.13 mg/kg b.w.) was administered daily for 13 days to 3- and 18-month old Sprague-Dawley rats and oral VOSO(4) was given from the 5th day. Plasma glucose, insulin and free fatty acids (FFA) concentrations were measured during these treatments and the insulin secretory response of the isolated perfused pancreas was assessed at the end of the experiment.


CONCLUSIONS
In both young and aging rats, particularly in the latter, hyperinsulinemia and increased in vitro insulin responsiveness to glucose were observed in response to Dex treatment, concomitant with an increase in plasma FFA concentrations. Thus, in glucocorticoid-treated animals, the beta-cell adaptive response occurred in both age groups and could possibly be mediated by increased circulating FFA; however, it was insufficient to prevent hyperglycemia in 60% of aging animals. Oral VOSO(4) administration failed to correct Dex-induced alterations in glucose and lipid metabolism, although it influenced in vitro beta-cell responsiveness to stimuli in aging rats.
Barbera
M
M
Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia e Epidemiologia, Universita degli Studi di Pisa, I-56126 Pisa, Italy.
Fierabracci
V
V
Novelli
M
M
Bombara
M
M
Masiello
P
P
Bergamini
E
E
De Tata
V
V
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000222:Adaptation, Physiological; D000311:Adrenal Glands / Q000033:anatomy & histology; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003907:Dexamethasone / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017968:Vanadium Compounds / Q000494:pharmacology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D007328:Insulin; D017968:Vanadium Compounds; C034028:vanadyl sulfate; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine