Identification and metabolism of polyphosphoinositides in isolated islets of Langerhans.
Isolated islets were incubated with [32P]P1 and radiolabelling of polyphosphoinositides were determined. Labelling equilibrium was approached after 45 min, with a half-time of 15 min. D-Glucose decreased the amount of [32P]PO4 in phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] and phosphatidylinositol 4-phosphate (PtdIns4P) within 0.5 min, and loss of radiolabel was still evident at 1 min. [32P]PO4 levels in polyphosphoinositides returned to basal levels within 5 min. Neither D-galactose nor D-glucose after pretreatment of islets with mannoheptulose elicited the polyphosphoinositide effect. The glucose-stimulated breakdown of polyphosphoinositides was inhibited by EGTA; re-addition of Ca2+ partially restored the glucose effect. Ionomycin and tolbutamide promoted the rapid breakdown of PtdIns(4,5)P2, whereas the breakdown of PtdIns4P was less rapid and of a lesser magnitude. The results suggest that the Ca2+-dependent breakdown of polyphosphoinositides in an early metabolic event during the initiation of insulin release.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D010710:Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D004533:Egtazic Acid; D008356:Mannoheptulose; D005947:Glucose; D002118:Calcium