MECHANISMS OF HORMONE ACTIONS
199
out that glucose uptake was being measured and not rate of penetration.
Glucose uptake is of course compounded of entry and metabolic transformation. Park has shown that at a low temperature at which hexokinase
activity was very strongly inhibited, the action of insulin on glucose
transfer could be shown readily (Park et al., 1955; Park and Johnson,
1955). Resnick and Hechter (1954), who used galactose to test the
transfer reaction in rat diaphragm, found insulin activity evident in N 2
as the gas phase. They have also demonstrated by paper chromatography
the presence of sufficient free galactose in the tissue to account for all
of the C
14 activity disappearing from the medium.
Even though galactose is not metabolized in the peripheral tissues of
the dog, and therefore is not removed after cell entry, insulin did not
lead to an accumulation against the gradient. The final concentration
was at equilibrium between the cell interior and the extracellular compartment. There is therefore no evidence for a so-called "active" transfer
mechanism.
The view as to the nature of the transfer system most consistent with
the data is that propounded by Höber (1927), namely, that "in addition
to the lipid elements one has to assume the existence of protoplasmic
areas of the cell surface which form the background for a regulated or
physiological permeability—a property of living tissue which it possesses
over and above physical' permeability."
From this standpoint insulin would have the property of combining
with a specific constituent of the surface of certain cells. As a consequence of such binding, a temporary distortion could be produced in the
molecular architecture of that surface, which would permit a greater
rate of entry to certain materials (the sugars) which exhibit a particular
kind of size, charge, etc. Brown (1952) found that "reactive points"
exist on the surface of plant root segments which permit entry of monosaccharides and that these "points" remain the same in number and
area even though the total surface increases. Goldacre (1952) discusses
the possibility of changes in protein configuration in relation to osmotic
work.
Insulin is not the only agent which facilitates sugar transfer. Clinical
experience and the more recent experimental work of Ingle (1951)
have shown that glucose utilization is increased and the blood sugar is
sharply reduced during muscular exercise in the complete absence of
insulin. Figures 9 and 10 show that muscular work leads to the transfer
into the cell of sugars which are themselves not utilized (Goldstein et al,
1953b). In other words, muscular work influences the cell surface system
in the same manner as does insulin (Figs. 9-10). It is suggested that
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