Cellular mechanisms of glucose-induced myo-inositol transport upregulation in rat mesangial cells. 1994

A A Chatzilias, and C I Whiteside
Department of Medicine, University of Toronto, Ontario, Canada.

Uptake of myo-inositol (MI) is necessary to maintain normal cellular phosphoinositide signaling and function. MI transport is up-regulated in the cells of diabetic rat glomeruli compared with normal rat glomeruli [C. I. Whiteside, J. C. Thompson, and J. Ohayon. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F138-F144, 1991]. To identify mechanisms associated with upregulation of MI transport, rat mesangial cells were cultured in high (25.6 mM) vs. normal (5.6 mM) glucose. Specific Na(+)-dependent [3H]MI uptake (> 97%), using L-[14C]glucose as the nonspecific marker, was linear for 120 min in high and normal glucose. In high glucose, compared with normal glucose, there was no change in Michaelis-Menten constant values [29.1 +/- 0.6 vs. 30.3 +/- 0.7 microM (SE)], whereas maximum velocity (Vmax) was increased (2.024 +/- 52 vs. 1.132 +/- 115 fmol.mg protein-1.min-1, P < 0.001). Mannitol (20.0 mM), used as an osmotic control, had no effect on the upregulation of MI transport. Maximum upregulation of MI transport measured by Vmax (control taken as 100%) was observed after 8 h of exposure to high glucose (222 +/- 6% above control, P < 0.0001) or galactose (20.0 mM) (194 +/- 6%, P < 0.0001) and was sustained for up to 48 h. The protein synthesis inhibitors cycloheximide (20 micrograms/ml) or actinomycin D (5 micrograms/ml), the F-actin depolymerizing agent cytochalasin D (2 micrograms/ml), and the aldose reductase inhibitor Tolrestat (0.3 mM) independently prevented glucose- or galactose-induced upregulation of MI transport.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007294 Inositol An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. Myoinositol,Chiro-Inositol,Mesoinositol,Chiro Inositol
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D005690 Galactose An aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood. D-Galactose,Galactopyranose,Galactopyranoside,D Galactose
D005920 Glomerular Mesangium The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX. Mesangium, Glomerular,Mesangial Extracellular Matrix,Extracellular Matrices, Mesangial,Extracellular Matrix, Mesangial,Glomerular Mesangiums,Matrices, Mesangial Extracellular,Matrix, Mesangial Extracellular,Mesangial Extracellular Matrices,Mesangiums, Glomerular
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000449 Aldehyde Reductase An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. Aldose Reductase,Aldose Reductase Ia,Aldose Reductase Ib,Erythrose Reductase,Xylose Reductase,Reductase Ia, Aldose,Reductase Ib, Aldose,Reductase, Aldehyde,Reductase, Aldose,Reductase, Erythrose,Reductase, Xylose
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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