Glucocorticoid increases glucose cycling and inhibits insulin release in pancreatic islets of ob/ob mice.
Normoglycemic ob/ob mice were treated for 24 or 48 h with either 25 micrograms/day of dexamethasone or saline. After an overnight fast, the animals were killed and pancreatic islets were incubated with 3H2O or [U-14C]glucose or [5-3H]glucose at 5.5 and 16.7 mM glucose. Incorporation of 3H from 3H2O into carbon 2 of medium glucose and the yield of 14CO2 from [U-14C]glucose and 3H2O from [5-3H]glucose were measured. Dexamethasone treatment for 48 h significantly increased the rate of dephosphorylation of glucose in islets both at 5.5 mM (24 vs. 16%) and 16.7 mM (56 vs. 36%) glucose, whereas glucose oxidation and utilization were unaffected. Dexamethasone treatment also inhibited insulin release by approximately 60% at 5.5 and 16.7 mM glucose, either in the presence or absence of 10 mM arginine, but had no effect when insulin release was stimulated by 1 mM 3-isobutyl-1-methylxanthine. Moreover, 24-h treatment with dexamethasone significantly increased glucose cycling at low and high glucose concentrations in the medium and inhibited insulin responsiveness to glucose and arginine. In conclusion, short-term dexamethasone treatment increases glucose flux through glucose-6-phosphatase in islets from ob/ob mice. This effect may contribute to the decreased insulin response to glucose and arginine found in animals treated with dexamethasone.
Khan
A
A
Rolf Luft Center for Diabetes Research, Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Ostenson
C G
CG
Berggren
P O
PO
Efendic
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D007329:Insulin Antagonists; D003907:Dexamethasone; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine