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Role of insulin receptor phosphorylation in the insulinomimetic effects of hydrogen peroxide

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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The oxidant H/sub 2/O/sub 2/ has many insulin-like effects in rat adipocytes. To determine whether these effects could be mediated by the tyrosine kinase activity of the insulin receptor, the ability of H/sub 2/O/sub 2/ to stimulate receptor phosphorylation in intact adipocytes and partially purified insulin receptors has been examined. Phosphorylation of the ..beta.. subunit of the insulin receptor was increased. Stimulation of receptor phosphorylation was rapid, reaching maximal levels within 5 min, and preceded activation of glucose transport. Phosphoamino acid analysis of insulin receptors from H/sub 2/O/sub 2/-treated adipocytes showed that /sup 32/P incorporation into phosphotyrosine and phosphoserine residues of the ..beta.. subunit was enhanced. Furthermore, partially purified receptors from H/sub 2/O/sub 2/-treated cells exhibit increased tyrosine kinase activity, as measured by phosphorylation of the peptide Glu/sub 80/Tyr/sub 20/. To define the factors involved in H/sub 2/O/sub 2/'s effect, the authors have examined receptor phosphorylation in fat cell homogenates and purified plasma membranes. Although insulin stimulated receptor phosphorylation in both of these systems, H/sub 2/O/sub 2/ was only effective in the cell homogenates. These data demonstrate that, under certain conditions, H/sub 2/O/sub 2/ stimulates insulin receptor phosphorylation and tyrosine kinase activity, suggesting that the insulin-like effects of H/sub 2/O/sub 2/ may be mediated by stimulation of insulin receptor phosphorylation. This does not appear to be a direct effect of H/sub 2/O/sub 2/ on the insulin receptor and requires nonplasma membrane cellular constituents.
Research Organization:
Univ. of Rochester School of Medicine and Dentistry, NY (USA)
OSTI ID:
6618723
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:22; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENZYME ACTIVITY
ENZYMES
FAT CELLS
HORMONES
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HORMONES
PEROXIDES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SOMATIC CELLS
TRANSFERASES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES