Cerebral Phosphoinositide and Energy Metabolism During and After Insulin‐Induced Hypoglycemia

Masuhiro Ikeda, Shinichi Yoshida, Raul Busto, Mercedes Santiso, Elena Martinez, Myron D. Ginsberg

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Abstract

During and after insulin-induced hypoglycemia, changes in levels of cerebral phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA), triacylglycerol (TAG), diacylglycerol (DAG), and free fatty acids (FFAs) as well as the cerebral energy state were studied in relation to the EEG. In hypoglycemic rats with an EEG pattern of quasiperiodic sharp or slow sharp waves, which preceded the development of an isoelectric EEG, PIP2 levels increased significantly, together with a slight decrease in PI content. Levels of the other lipids did not change during this period. The cerebral energy state was affected only slightly in spite of profound decreases in plasma and tissue glucose levels. With 30 min of an isoelectric EEG, levels of all phosphoinositides and PA decreased significantly; total FFA and DAG contents increased seven- and twofold, respectively; the TAG-palmitate level decreased, and that of TAG-arachidonate increased. Plasma and tissue glucose were nearly depleted, and the cerebral energy state deteriorated severely. The increment in fatty acids in the DAG and FFA pools was less than their loss from phosphoinositides and PA, an observation suggesting vascular washout or oxidation of a portion of the FFAs produced. Following 90 min of glucose infusion, PIP and PA levels recovered to control values; however, the PIP2 content exceeded control levels, and that of PI remained below control levels. DAG and FFA contents returned to normal. The data suggest that PIP2 synthesis is increased or PIP2 degradation is blocked because of disturbed neurotransmission during the preisoelectric and recovery periods, at a time when the tissue energy state is minimally affected, and that all phosphoinositides are degraded during the period of isoelectric EEG, probably owing to energy shortage.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalJournal of neurochemistry
Volume49
Issue number1
DOIs
StatePublished - Jul 1987

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Keywords

  • Free fatty acids
  • Hypoglycemia
  • Phosphoinositides
  • Rat brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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