Unimpaired formation of hormone-stimulated inositol trisphosphate in human mesangial cells under hyperglycemic conditions.
The relationship between bulk cellular myo-inositol content and phosphatidylinositol metabolism was evaluated in a human mesangial cell line under euglycemic and hyperglycemic conditions. Mesangial cells maintained in high glucose medium displayed a concentration-dependent fall in myo-inositol as measured by gas-liquid chromatography. Measurements of phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate mass revealed slight but statistically insignificant increases in cells exposed to high glucose containing medium. CDP-diacylglycerol: myo-inositol 3-phosphatidylinositol transferase activity, measured in plasma membranes from mesangial cells grown under control and hyperglycemic conditions, was kinetically similar with Michaelis constants (Km values) for myo-inositol of 2.9 and 2.1 mM, respectively. Finally, hormone-stimulated intracellular calcium mobilization and myo-inositol 1,4,5-trisphosphate mass was measured from mesangial cells grown under normal and hyperglycemic conditions. Both intracellular calcium and inositol trisphosphate formation were unchanged in cells previously exposed to high glucose conditions (400 mg/dl) compared to cells grown under normal glucose concentration (100 mg/dl). These data indicate that bulk changes in myo-inositol induced by hyperglycemia are neither associated with alterations in basal levels of inositol containing glycerolipids nor with changes in hormone-stimulated calcium mobilization and inositol trisphosphate formation under conditions of short term changes in extracellular glucose.
Greenberg
L
L
Department of Internal Medicine, University of Michigan, Ann Arbor.
Urbanes
A Q
AQ
Shayman
J A
JA
D001920:Bradykinin / Q000494:pharmacology; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002845:Chromatography; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007700:Kinetics; D008565:Membrane Proteins; D010716:Phosphatidylinositols / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups); D014667:Vasopressins / Q000494:pharmacology
D008565:Membrane Proteins; D010716:Phosphatidylinositols; D014667:Vasopressins; D007294:Inositol; D015544:Inositol 1,4,5-Trisphosphate; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C496766:CDIPT protein, human; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D005947:Glucose; D001920:Bradykinin; D002118:Calcium