Relationships between energy level and insulin secretion in isolated rat islets of Langerhans. Manipulation of [ATP]/[ADP][Pi] by 2-deoxy-D-glucose.
Perifusion of islets with nominally phosphate-free buffer containing increasing concentrations of 2-deoxy-D-glucose (2.5 to 10 mM) produced increments in high alpha-ketoisocaproic acid-induced secretion of insulin beyond those observed in the absence of the sugar analogue. 3-O-methyl-D-glucose, a poorly metabolized sugar, was without effect. Insulin release evoked by 40 mM KCl was not altered by 2-deoxyglucose. The concentration of intracellular inorganic phosphate was lower in islets perifused with 2-deoxyglucose and declined to a lower level after addition of 20 mM alpha-ketoisocaproic acid. The enhancement of alpha-ketoisocaproic acid-induced hormone secretion by 2-deoxyglucose was not seen in islets perifused with medium containing 1.5 mM phosphate; instead a small inhibition was observed. It is postulated that conditions which lower intracellular [Pi] facilitate, either directly or indirectly, hormone release although the mechanism of this effect remains to be elucidated.
Ohta
M
M
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
Nelson
D
D
Wilson
J M
JM
Meglasson
M D
MD
Erecińska
M
M
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology*; D004734:Energy Metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010710:Phosphates / Q000032:analysis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D007328:Insulin; D007651:Keto Acids; D010710:Phosphates; C013082:alpha-ketoisocaproic acid; D003847:Deoxyglucose