Direct effect of insulin on the synthesis of specific plasma proteins: biphasic response of hepatocytes cultured in serum- and hormone-free medium.

Monolayers of chicken embryo hepatocytes. cultured in chemically defined medium, retain the ability to synthesize a wide spectrum of plasma proteins for several days in the absence of added hormones. Addition of insulin to the medium elicited a biphasic stimulation of plasma protein synthesis: a rapid response of the synthesis of a limited number of plasma proteins (e.g., albumin and alpha 1-globulin "M"), then, after prolonged exposure to the hormone, the involvement of additional plasma proteins (e.g., fibrinogen and lipoproteins). Synthesis of transferrin and a few other plasma proteins was not affected by the presence of insulin. The degree of stimulation for the most response plasma proteins ranged between 2- to 4-fold during the early phase and 10- and even 30-fold during the late phase of the cells' response t insulin. Stimulated synthesis in the early phase was detected within 1 hr and was rapidly reversible. Plasma protein synthesis in culture was sensitive to concentrations of insulin below 0.35 nM, well within the physiological range. The delayed response was elicited only at higher hormone levels. Parallels between the control of synthesis of plasma proteins in this system and that observed in diabetic animals suggest that the embryonic chicken hepatocytes may be a useful model for studying liver function in diabetes as well as insulin action in general.