Developmental aspects of the rat brain insulin receptor: loss of sialic acid and fluctuation in number characterize fetal development
In this study, I have investigated the structure of the rat brain insulin receptor during fetal development. There is a progressive decrease in the apparent molecular size of the brain alpha-subunit during development: 130K on day 16 of gestation, 126K at birth, and 120K in the adult. Glycosylation was investigated as a possible reason for the observed differences in the alpha-subunit molecular size. The results show that the developmental decrease in the brain alpha-subunit apparent molecular size is due to a parallel decrease in sialic acid content. This was further confirmed by measuring the retention of autophosphorylated insulin receptors on wheat germ agglutinin (WGA)-Sepharose. An inverse correlation between developmental age and retention of /sup 32/P-labeled insulin receptors on the lectin column was observed. Insulin binding increases 6-fold between 16 and 20 days of gestation (61 +/- 25 (+/- SE) fmol/mg protein and 364 +/- 42 fmol/mg, respectively). Thereafter, binding in brain membranes decreases to 150 +/- 20 fmol/mg by 2 days after birth, then reaches the adult level of 63 +/- 15 fmol/mg. In addition, the degree of insulin-stimulated autophosphorylation closely parallels the developmental changes in insulin binding. Between 16 and 20 days of fetal life, insulin-stimulated phosphorylation of the beta-subunit increases 6-fold. Thereafter, the extent of phosphorylation decreases rapidly, reaching adult values identical with those in 16-day-old fetal brain. These results suggest that the embryonic brain possesses competent insulin receptors whose expression changes markedly during fetal development. This information should be important in defining the role of insulin in the developing nervous system.
- Research Organization:
- Harvard Univ., Cambridge, MA (USA)
- OSTI ID:
- 6975156
- Journal Information:
- Endocrinology; (United States), Vol. 122:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INSULIN
BIOCHEMICAL REACTION KINETICS
RECEPTORS
MOLECULAR STRUCTURE
SIALIC ACID
BIOSYNTHESIS
AGE DEPENDENCE
BRAIN
CELL MEMBRANES
FETUSES
MOLECULAR WEIGHT
OLIGOSACCHARIDES
PHOSPHORUS 32
PHOSPHORYLATION
RATS
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
HORMONES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MONOSACCHARIDES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SACCHARIDES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques