Effect of insulin on GABAergic development in the embryonic chick retina.
We investigated the role of insulin in GABAergic differentiation in the embryonic chick retina at different embryonic ages using glutamate decarboxylase (GAD) and high-affinity GABA uptake as developmental markers. Both these GABAergic markers exhibit developmentally programmed increases in activity during retinogenesis that also occur in culture. Insulin stimulated GABA uptake in retina neurons at all embryonic ages in a dose-dependent manner and GAD activity by 30% in embryonic retina neurons after 11 days of development. The stimulation of GABA uptake by insulin was blocked by addition of ouabain suggesting a role for the Na+,K+ ATPase. The same concentration of insulin caused a 76% stimulation of protein synthesis in these retinal cells, and previous work demonstrated that insulin also stimulates cholinergic differentiation in the chick retina (Hausman et al., Dev. Brain. Res. 59, (1991) 31-37). Thus, there was no selective stimulation of GABAergic differentiation by insulin but likely a neurotrophic effect. The increase in GAD activity in neurons from post-11-day embryonic neurons contrasts with our previous findings at embryonic days 6-7 where there is little change in GAD activity after addition of insulin. It is possible that the failure of insulin to stimulate GAD activity during early retina development is due to the increased accumulation of GABA in the presence of insulin. GABA levels were increased more than two-fold by 100 ng/ml insulin.
Shah
B H
BH
Department of Biology, Boston University, MA 02215.
Hausman
R E
RE
D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D007328:Insulin; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase