Metabolic, cationic and secretory response to D-glucose in depolarized and Ca(2+)-deprived rat islets exposed to diazoxide.
D-glucose stimulates insulin release from islets exposed to both diazoxide, to activate ATP-responsive K+ channels, and a high concentration of K+, to cause depolarization of the B-cell plasma membrane. Under these conditions, the insulinotropic action of D-glucose is claimed to occur despite unaltered cytosolic Ca2+ concentration, but no information is so far available on the changes in Ca2+ fluxes possibly caused by the hexose. In the present experiments, we investigated the effect of D-glucose upon 45Ca efflux from islets exposed to both diazoxide and high K+ concentrations. In the presence of diazoxide and at normal extracellular Ca2+ concentration, D-glucose (16.7 mmol/l) inhibited insulin release at 5 mmol/l K+, but stimulated insulin release of 90 mmol/l K+. In both cases, the hexose inhibited 45Ca outflow. In the presence of diazoxide, but absence of Ca2+, D-glucose (8.3 to 25.0 mmol/l) first caused a rapid decrease in insulin output followed by a progressive increase in secretory rate. This phenomenon was observed both at 5 mmol/l or higher concentrations (30, 60 and 90 mmol/l) of extracellular K+. It coincided with a monophasic decrease in 45Ca efflux and either a transient (at 5 mmol/l K+) or sustained (at 90 mmol/l K+) decrease in overall cytosolic Ca2+ concentration. The decrease in 45Ca efflux could be due to inhibition of Na(+)-Ca2+ countertransport with resulting localized Ca2+ accumulation in the cell web of insulin-producing cells. A comparable process may be involved in the secretory response to D-glucose in islets exposed to diazoxide and a high concentration of K+ in the presence of extracellular Ca2+.
Lebrun
P
P
Laboratory of Pharmacology, Brussels Free University, Belgium.
Antoine
M H
MH
Nguyen
Q A
QA
Picton
S
S
Malaisse
W J
WJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006601:Hexoses / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats
D006601:Hexoses; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D005905:Glyburide; D002118:Calcium