7. C A R B O H Y D R A T E A N D E N E R G Y M E T A B O L I S M
265
and Krichevskaya, 1960; Leslie, Fulton and Sinclair, 1957; Paul and
Pearson, 1960). The effects reported are, however, somewhat marginal,
although the insulin concentrations employed have usually been rather
high (10~
2
-1 unit per ml). It has been suggested that this may be due
to the rapid destruction of insulin in the culture medium (Chen, 1954;
Vallance-Owen, Hurlock and Please, 1955). Also, different cells may
respond differently and, in particular, Leslie et al. reported that strains
of cancerous origin were more responsive to insulin (Leslie, Fulton and
Sinclair, 1956, 1957). Even when allowance is made for these factors, it
seems nevertheless that the sensitivity of cell strains to insulin is very
low. By contrast in organ cultures of brown fat of rats a pronounced
effect on carbohydrate uptake, lipid and carbohydrate storage, has been
observed when the cultures are only briefly exposed to dilute insulin
(0-04 jLtg/ml) (Sidman, 1956, and see Vol. 3, Chapter 7).
Gey and Thalhimer (1924) and V o n Haam and Cappel (1941)
originally reported that insulin had a growth-promoting effect in
primary explant cultures. Later Leslie and Paul (1954) demonstrated
this effect in primary cultures of chick heart. When attempts to reproduce these results were made with continuously cultivated strains little
success was generally obtained although a growth-stimulating effect has
been reported in at least one instance (Lieberman and Ove, 1959). The
phenomenon is inconstant and elusive and the factors involved have
not been clearly identified.
Paul and Pearson (1960) reported that insulin stimulated pinocytosis
in HeLa cells. The observation is of some interest since ChapmanAndresen and Holter (1955) have shown that the uptake of glucose by
the amoeba, Chaos chaos, is greatly increased if pinocytosis is induced.
Although Paul and Pearson were cautious about accepting this interpretation, the work of Barrnett and Ball (1960) perhaps gives it more
substance, since they were able to show that, in epididymal adipose
tissue of the rat, insulin induces an intense vacuolation near the cell
membrane, which later extends throughout the cell and is almost
certainly due to pinocytosis. This effect was produced by 0-004 /xg/ml.
It is inviting, therefore, to speculate that insulin may act by promoting increased glucose absorption, perhaps by means of pinocytosis
and that the demonstration of other effects may depend on the metabolic
potentialities of the cell and the factors which are limiting at the time.
(b) Corticosteroids. Few meaningful results have been obtained by
treating cell cultures with corticosteroids and the only fact which has
been established with certainty is that in high concentrations they
inhibit growth and respiration and stimulate glycolysis (Grossfeld,
1958).
(c) Thyroid hormones. Again little useful information has been obtained
K*
265
and Krichevskaya, 1960; Leslie, Fulton and Sinclair, 1957; Paul and
Pearson, 1960). The effects reported are, however, somewhat marginal,
although the insulin concentrations employed have usually been rather
high (10~
2
-1 unit per ml). It has been suggested that this may be due
to the rapid destruction of insulin in the culture medium (Chen, 1954;
Vallance-Owen, Hurlock and Please, 1955). Also, different cells may
respond differently and, in particular, Leslie et al. reported that strains
of cancerous origin were more responsive to insulin (Leslie, Fulton and
Sinclair, 1956, 1957). Even when allowance is made for these factors, it
seems nevertheless that the sensitivity of cell strains to insulin is very
low. By contrast in organ cultures of brown fat of rats a pronounced
effect on carbohydrate uptake, lipid and carbohydrate storage, has been
observed when the cultures are only briefly exposed to dilute insulin
(0-04 jLtg/ml) (Sidman, 1956, and see Vol. 3, Chapter 7).
Gey and Thalhimer (1924) and V o n Haam and Cappel (1941)
originally reported that insulin had a growth-promoting effect in
primary explant cultures. Later Leslie and Paul (1954) demonstrated
this effect in primary cultures of chick heart. When attempts to reproduce these results were made with continuously cultivated strains little
success was generally obtained although a growth-stimulating effect has
been reported in at least one instance (Lieberman and Ove, 1959). The
phenomenon is inconstant and elusive and the factors involved have
not been clearly identified.
Paul and Pearson (1960) reported that insulin stimulated pinocytosis
in HeLa cells. The observation is of some interest since ChapmanAndresen and Holter (1955) have shown that the uptake of glucose by
the amoeba, Chaos chaos, is greatly increased if pinocytosis is induced.
Although Paul and Pearson were cautious about accepting this interpretation, the work of Barrnett and Ball (1960) perhaps gives it more
substance, since they were able to show that, in epididymal adipose
tissue of the rat, insulin induces an intense vacuolation near the cell
membrane, which later extends throughout the cell and is almost
certainly due to pinocytosis. This effect was produced by 0-004 /xg/ml.
It is inviting, therefore, to speculate that insulin may act by promoting increased glucose absorption, perhaps by means of pinocytosis
and that the demonstration of other effects may depend on the metabolic
potentialities of the cell and the factors which are limiting at the time.
(b) Corticosteroids. Few meaningful results have been obtained by
treating cell cultures with corticosteroids and the only fact which has
been established with certainty is that in high concentrations they
inhibit growth and respiration and stimulate glycolysis (Grossfeld,
1958).
(c) Thyroid hormones. Again little useful information has been obtained
K*