198
RACHMIEL LEVINE
in the "fixed" state. This work has also emphasized the need for a degree
of "intactness" of the cell in demonstrating certain hormonal activities.
These data and views are compatible with the theory of insulin action
here presented, but provide as yet no additional insight into the nature
of the "transfer" system.
The nature and chemical structure of what is loosely called the cell
membrane or surface is, in the case of most animal cells, still in the realm
of concept and speculation. Its lipoprotein constitution is derived from
studies on red cell "ghosts" and deductions based upon rates of penetration in relation to lipid solubility. Rosenberg and Wilbrandt (1952)
have recently reviewed the literature on red cell permeability to the
sugars. Their own work, together with that of Rothstein (1954), leads
them to the conclusion that glucose is phosphorylated at the surface to
a metaphosphate form, which is more lipid-soluble and thus gains entry
into the cell. There is no direct evidence that phosphorylation precedes
entry (Sacks and Sinex, 1953) but this work and that of Le Fevre and
Davies (1951) and Widdas (1954) suggests that specific constituents
of the cell surface are concerned with the transport of certain sugars.
It is interesting to note that the structural specificity of the insulin-responsive sugars is reflected in a similar specificity of red cell permeability.
Wilbrandt (1950) remarks that in the case of human erythrocytes
L-arabinose and D-xylose penetrate, but the cells are not permeable to
D-arabinose and L-xylose. Widdas (1954) suggests that the present
evidence is compatible with a "carrier" type of entry followed by phosphorylation. Inhibition by phlorizin (Widdas, 1954) does not prove
phosphorylation. This glucoside may be a competitive inhibitor because
of its structural relation to sugars.
In muscle tissue galactose, xylose, and arabinose have not been shown
to become phosphorylated. At the height of insulin action on galactose
distribution, P
32
turnover is not increased over that of the noninsulin
period.
Using rat diaphragm in vitro at several temperatures between 10 °C
and 37.5 °C it could be ascertained that the action of insulin in facilitating sugar entry had a Q 10 of only 1.2. This suggests that the action is
exerted on a system different in its behavior from an "enzyme" and that
the process is attended by little or no energy exchange. It is true that
muscle kept for a time in the anaerobic state shows less (Walaas and
Walaas, 1952) or no insulin activity (Dennis and Rothstein, 1954) in
promoting glucose uptake. But this does not necessarily argue for a
process coupled with oxidation. Reaction of insulin with the specific cell
constituent may be impossible in an atmosphere of N 2 because of reduction of some important group in the molecule. It should also be pointed
RACHMIEL LEVINE
in the "fixed" state. This work has also emphasized the need for a degree
of "intactness" of the cell in demonstrating certain hormonal activities.
These data and views are compatible with the theory of insulin action
here presented, but provide as yet no additional insight into the nature
of the "transfer" system.
The nature and chemical structure of what is loosely called the cell
membrane or surface is, in the case of most animal cells, still in the realm
of concept and speculation. Its lipoprotein constitution is derived from
studies on red cell "ghosts" and deductions based upon rates of penetration in relation to lipid solubility. Rosenberg and Wilbrandt (1952)
have recently reviewed the literature on red cell permeability to the
sugars. Their own work, together with that of Rothstein (1954), leads
them to the conclusion that glucose is phosphorylated at the surface to
a metaphosphate form, which is more lipid-soluble and thus gains entry
into the cell. There is no direct evidence that phosphorylation precedes
entry (Sacks and Sinex, 1953) but this work and that of Le Fevre and
Davies (1951) and Widdas (1954) suggests that specific constituents
of the cell surface are concerned with the transport of certain sugars.
It is interesting to note that the structural specificity of the insulin-responsive sugars is reflected in a similar specificity of red cell permeability.
Wilbrandt (1950) remarks that in the case of human erythrocytes
L-arabinose and D-xylose penetrate, but the cells are not permeable to
D-arabinose and L-xylose. Widdas (1954) suggests that the present
evidence is compatible with a "carrier" type of entry followed by phosphorylation. Inhibition by phlorizin (Widdas, 1954) does not prove
phosphorylation. This glucoside may be a competitive inhibitor because
of its structural relation to sugars.
In muscle tissue galactose, xylose, and arabinose have not been shown
to become phosphorylated. At the height of insulin action on galactose
distribution, P
32
turnover is not increased over that of the noninsulin
period.
Using rat diaphragm in vitro at several temperatures between 10 °C
and 37.5 °C it could be ascertained that the action of insulin in facilitating sugar entry had a Q 10 of only 1.2. This suggests that the action is
exerted on a system different in its behavior from an "enzyme" and that
the process is attended by little or no energy exchange. It is true that
muscle kept for a time in the anaerobic state shows less (Walaas and
Walaas, 1952) or no insulin activity (Dennis and Rothstein, 1954) in
promoting glucose uptake. But this does not necessarily argue for a
process coupled with oxidation. Reaction of insulin with the specific cell
constituent may be impossible in an atmosphere of N 2 because of reduction of some important group in the molecule. It should also be pointed