Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes
The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 mycocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with (/sup 32/P)NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on (/sup 3/H)thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated (/sup 3/H)thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin.
- Research Organization:
- Univ. of Virginia School of Medicine, Charlottesville (USA)
- OSTI ID:
- 6925014
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 263:13
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INSULIN
BIOCHEMISTRY
TOXINS
BIOLOGICAL EFFECTS
TRITIUM COMPOUNDS
UPTAKE
ANIMAL CELLS
CELL DIFFERENTIATION
DOSE-RESPONSE RELATIONSHIPS
GLUCOSE
MICE
MUSCLES
TETRADECANOIC ACID
THYMIDINE
ALDEHYDES
ANIMALS
ANTIGENS
AZINES
CARBOHYDRATES
CARBOXYLIC ACIDS
CHEMISTRY
HETEROCYCLIC COMPOUNDS
HEXOSES
HORMONES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PYRIMIDINES
RIBOSIDES
RODENTS
SACCHARIDES
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques