Production of inositol trisphosphates and inositol tetrakisphosphate in stimulated pancreatic islets.

Glucose and carbamylcholine caused concentration-dependent increases in the production of total [3H]inositol phosphates in [3H]inositol-labelled rat pancreatic islets. When extracts from islets stimulated with glucose, carbamylcholine or depolarising concentrations of K+ were analysed using anion-exchange high performance liquid chromatography, increased production of [3H]Ins1,4,5-P3 was detected, and in addition, elevated levels of two other labelled compounds which co-chromatographed with Ins1,3,4-P3 and Ins1,3,4,5-P4. In the case of carbamylcholine and high K+, such an effect was apparent within 20 s, whereas glucose appeared to cause a delayed response. In the presence of 5 mM LiCl, the accumulation of Ins1,3,4-P3 was more marked. The presence of LiCl had no major influence on the levels of Ins1,4,5-P3 or Ins1,3,4,5-P4. It is suggested that the stimulation of pancreatic islets with glucose, carbamylcholine or high K+ results in the hydrolysis of inositol lipids with the production of Ins1,4,5-P3 and in addition, Ins1,3,4-P3 and Ins1,3,4,5-P4. The physiological functions of these novel inositol phosphates in islets remain to be established.