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Nutrient and hormone-neurotransmitter stimuli induce hydrolysis of polyphosphoinositides in rat pancreatic islets

Journal Article · · Endocrinology; (United States)

Preincubation of rat pancreatic islets with /sup 3/H-inositol, and subsequent exposure, in the presence of LiCl, to either glucose or carbamylcholine resulted in a rapid stimulation of /sup 3/H-inositol 1,4,5-triphosphate and /sup 3/H-myo-inositol 1,4-bisphosphate formation, the level of which reached a plateau after about 5 min of stimulation. Both stimuli also caused an approximately linear accumulation of /sup 3/H-myo-inositol 1-phosphate. The amounts of /sup 3/H-inositol phosphates formed were dependent on the concentration of LiCl. Studies of /sup 32/P-labeling of islet ATP, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and phosphatidylinositol 4-phosphate revealed that these approached isotopic equilibrium after about 240-min incubation, whereas /sup 32/P-labeling of phosphatidylinositol, phosphatidic acid, phosphatidylcholine, and phosphatidylethanolamine proceeded at a lower rate. Carbamylcholine provoked an immediate fall in /sup 32/P-PtdIns(4,5)P2 and, to a lesser extent, /sup 32/P-phosphatidylinositol 4-phosphate. Glucose caused a similar response although, in this case, the most marked decline was in a more polar /sup 32/P-labeled lipid. Cholecystokinin-pancreozymin was also found to induce /sup 32/P-PtdIns(4,5)P2 hydrolysis, although the ionophore A23187 was without effect. Both carbamylcholine and glucose induced an increase in /sup 32/P-phosphatidic acid. The results provide two independent pieces of evidence suggesting that phospholipase C-mediated hydrolysis of polyphosphoinositides occurs as an early response in rat islets to either nutrient or neurotransmitter secretagogues.

Research Organization:
Brussels Free Univ., Belgium
OSTI ID:
6006012
Journal Information:
Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 115:5; ISSN ENDOA
Country of Publication:
United States
Language:
English

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