188
RACHMIEL LEVINE
Using the eviscerated spinal cat preparation, they could account for
the glucose disappearing under "the action of insulin" by an increase in
muscle glycogen and by oxidation (assuming that all of the 0 2 consumed
was used for oxidation of sugar). From their data it is apparent that
the major quantitative effect of insulin in this preparation was the
increase in muscle glycogen.
In view of all the effects of insulin which have been observed over
the years, the fall in blood sugar and the increase of skeletal muscle
glycogen (in the presence of glucose) are the effects characterized by
the greatest consistency and least controversy. We shall return to a
discussion of the contradictory data on the effects of insulin and glucose
on liver uptake of sugar and liver storage of glycogen, as seen in the
light of our present-day knowledge. At this point, however, we may
take it as uncontroverted that, under the influence of insulin, skeletal
muscle in vivo takes in more glucose from the blood and deposits more
glycogen than in the absence of added insulin. The data of Bridge
(1938) (Fig. 1) on the intact normal rabbit and the work from Lundsgaard's laboratory (Lundsgaard et al, 1936) on perfused hind limbs
demonstrate these facts.
In 1937, Soskin and Levine drew attention to the fact that the rate of
uptake of sugar by the extrahepatic tissues of the dog depended upon
the height of the blood sugar level maintained by the animal. This was
true for the depancreatized animal (complete absence of insulin), the
normal animal (endogenous insulin), and the insulinized normal animal
(excess insulin). The defect exhibited by the peripheral tissues of the
depancreatized animal consisted of a reduction in rate of glucose uptake
at any but the highest blood sugar levels. On the other hand, a rise in
blood sugar level (increased sugar pressure, so to speak) could compensate for the lack of the hormone. It was therefore concluded at that
time that insulin was not absolutely essential for sugar disposal, but that
it facilitated it by bringing it faster into the intermediary scheme of
metabolic disposal of carbohydrate in the cell (Soskin and Levine, 1940).
In conformity with the concepts of the enzymatic scheme, it was postulated that "insulin facilitates the formation from glucose of an intermediate substance (phosphorylated hexose?) which precedes and is
necessary for both catabolism and synthesis" (Soskin and Levine, 1940).
The relationship between the level of blood sugar and its rate of
disappearance into the tissues was observed by Lundsgaard et al. (1939)
in the isolated hind limbs of cats and rabbits; and by Villee and Hastings (1949) in rat diaphragm in vivo taken from normal as well as
alloxan-diabetic animals. The significance of these observations lies in
the fact that they offer a means of distinguishing between the "primary"
RACHMIEL LEVINE
Using the eviscerated spinal cat preparation, they could account for
the glucose disappearing under "the action of insulin" by an increase in
muscle glycogen and by oxidation (assuming that all of the 0 2 consumed
was used for oxidation of sugar). From their data it is apparent that
the major quantitative effect of insulin in this preparation was the
increase in muscle glycogen.
In view of all the effects of insulin which have been observed over
the years, the fall in blood sugar and the increase of skeletal muscle
glycogen (in the presence of glucose) are the effects characterized by
the greatest consistency and least controversy. We shall return to a
discussion of the contradictory data on the effects of insulin and glucose
on liver uptake of sugar and liver storage of glycogen, as seen in the
light of our present-day knowledge. At this point, however, we may
take it as uncontroverted that, under the influence of insulin, skeletal
muscle in vivo takes in more glucose from the blood and deposits more
glycogen than in the absence of added insulin. The data of Bridge
(1938) (Fig. 1) on the intact normal rabbit and the work from Lundsgaard's laboratory (Lundsgaard et al, 1936) on perfused hind limbs
demonstrate these facts.
In 1937, Soskin and Levine drew attention to the fact that the rate of
uptake of sugar by the extrahepatic tissues of the dog depended upon
the height of the blood sugar level maintained by the animal. This was
true for the depancreatized animal (complete absence of insulin), the
normal animal (endogenous insulin), and the insulinized normal animal
(excess insulin). The defect exhibited by the peripheral tissues of the
depancreatized animal consisted of a reduction in rate of glucose uptake
at any but the highest blood sugar levels. On the other hand, a rise in
blood sugar level (increased sugar pressure, so to speak) could compensate for the lack of the hormone. It was therefore concluded at that
time that insulin was not absolutely essential for sugar disposal, but that
it facilitated it by bringing it faster into the intermediary scheme of
metabolic disposal of carbohydrate in the cell (Soskin and Levine, 1940).
In conformity with the concepts of the enzymatic scheme, it was postulated that "insulin facilitates the formation from glucose of an intermediate substance (phosphorylated hexose?) which precedes and is
necessary for both catabolism and synthesis" (Soskin and Levine, 1940).
The relationship between the level of blood sugar and its rate of
disappearance into the tissues was observed by Lundsgaard et al. (1939)
in the isolated hind limbs of cats and rabbits; and by Villee and Hastings (1949) in rat diaphragm in vivo taken from normal as well as
alloxan-diabetic animals. The significance of these observations lies in
the fact that they offer a means of distinguishing between the "primary"