Ontogenesis of the Insulin Receptor in the Rabbit Brain

Abstract

We delineated the ontogeny of the brain insulin binding, insulin receptor number and affinity using plasma membranes isolated from the rabbit. Specific ¹²⁵I-insulin binding and receptor number expressed per milligram of protein increased from the 20 day gestation fetus to the 1-day-old newborn, declining thereafter to attain adult values by day 6 of postnatal life. Specific ¹²⁵I-insulin binding and the receptor number in the adult brain was less than the fetal and neonatal (1 day) brain receptors. Although a similar trend was observed specifically during fetal development, the changes in receptor number expressed per microgram DNA were not significant in the neonatal period. The adult brain insulin receptor number was higher than the 20- to 27-day fetus and similar to that of the 30-day fetus and the 1- to 5-day newborns. The total receptor number correlated linearly with the brain plasma membrane protein increment velocity. The affinity of the receptors increased during early fetal development (20–27 days) and remained constant thereafter in the postnatal period. We conclude that the ontogenic changes of the brain insulin receptors are similar to the ontogenic changes of brain plasma membrane protein. The developmental changes are more pronounced when the receptor number is expressed per milligram protein versus microgram DNA.

Ontogeny of Insulin Binding in Different Regions of the Rat Brain

“…Most studies have used membranes prepared from whole brain [8][9][10]26] and are therefore most comparable to our results for cerebral cortex, which is the major con tributor to brain protein. Our results show that studies using whole brain mask the con siderable variation in regional developmen tal changes of insulin binding.…”

“…Previous studies of insulin binding during rat and rabbit brain development have also shown maximal levels in the early postnatal period [10,26], although maximal levels at earlier [8] and later times [27] have been re ported. Most studies have used membranes prepared from whole brain [8][9][10]26] and are therefore most comparable to our results for cerebral cortex, which is the major con tributor to brain protein.…”

Insulin, Aging, and the Brain: Mechanisms and Implications

“…Insulin was found to be present in high concentrations in brain micro-vessels ( 38 ), brain extracts ( 39 ), and immature nerve cell bodies ( 35 , 40 ), despite that only 0.046% of peripheral insulin crosses the BBB in mice ( 12 , 41 ). Moreover, brain insulin concentrations were observed to vary according to developmental stages, with peak amounts being observed during the critical phases of brain growth and development ( 42 ). Taken together, these results suggest that brain insulin availability is strictly regulated and can reach high levels in the CNS.…”

Plasma constituents and mortality in rat pups given chronic insulin via injection, pellet, or osmotic minipump

“…Several investigators have examined the ontogeny of insulin's appearance and actions. Insulin appears to facilitate the development of brain tissue by aiding the processes of brain myelination and glial differentiation (Sena and Ferret-Sena 1995), and fetal concentrations of circulating brain insulin are higher than neonatal or adult values in rats, mice, and rabbits (Bernstein et al 1984;Devaskar et al 1986;Schechter et al 1992). Insulin then begins to play a role in the regulation of food intake, acting as both a satiety hormone (Anika et al 1980;VanderWeele 1994) and a trigger for food intake when present at elevated levels (Brandes 1977;Tordoff et al 1982).…”