DNA-synthesis regulation and correlation with inositol trisphosphate levels in cultured bovine retinal capillary pericytes

Exp Eye Res. 1989 Oct;49(4):677-83. doi: 10.1016/s0014-4835(89)80062-4.


Inositol phosphate (IP), inositol bisphosphate (IP2) and inositol trisphosphate (IP3) in cultured bovine retinal capillary pericytes (BRCP) were quantitated by an ion-pair reverse-phase HPLC. BRCP were grown in media with standard (5 mM) or high (30 mM) glucose, and were either labeled with myo-[2-3H]inositol (20 microCi ml-1) for 60 hr or with dual isotopes (20 microCi ml-1 myo-[2-3H]inositol and 2 microCi ml-1 [14C]glycerol) for 8 hr. In parallel, BRCP in different glucose-media were incubated with 1 microCi ml-1 [3H]thymidine for 4 hr. High glucose significantly suppressed the accumulation of [3H]label in IP, IP2 and IP3, and specifically reduced the incorporation of [14C]glycerol into inositol phospholipids, but not that of neutral lipids and other types of phospholipids. The reduced IP3 level correlated with the decrease in the incorporation of [3H]thymidine into DNA. Both the reduced IP3 formation and DNA synthesis which were induced by high glucose were significantly reversed by adding either myo-inositol or AL1576, an aldose reductase inhibitor (ARI). However, the addition of neither myo-inositol nor ARI stimulated IP3 formation and/or DNA synthesis when BRCP were grown in the standard medium (5 mM glucose). These findings indicate that myo-inositol metabolism and the polyol pathway affect inositol phospholipid-mediated pericyte division in vitro only under the high-glucose condition. These data are compatible with the hypothesis that altered inositol phospholipid metabolism accounts for the loss of pericytes in diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cattle
  • Cells, Cultured
  • DNA / biosynthesis*
  • Inosine Nucleotides / metabolism*
  • Inosine Triphosphate / metabolism*
  • Inositol Phosphates / metabolism
  • Retinal Vessels / cytology
  • Retinal Vessels / metabolism*


  • Inosine Nucleotides
  • Inositol Phosphates
  • Inosine Triphosphate
  • DNA