COMMENTARY
Recycling of glucose and determination of the Cori Cycle and
gluconeogenesis
Joseph
Katz and
John A.
Tayek
Department of Internal Medicine, Harbor-University of California
Los Angeles Medical Center, Torrance, California 90502
 |
ABSTRACT |
We have derived equations, by employing
[U-13C]glucose and
mass isotopomer analysis, to determine the pathways of glycogen
synthesis (J. Katz, W. P. Lee, P. A. Wals, and E. A. Bergner.
J. Biol. Chem. 264: 12994-13004,
1989). More recently, by use of these methods we have derived equations
to determine the rate of glucose recycling and of gluconeogenesis
[Tayek and Katz. Am. J. Physiol.
270 (Endocrinol. Metab. 33):
E709-E717, 1996 and 272 (Endocrinol.
Metab. 35): E476-E484, 1997, and Katz and Tayek.
Am. J. Physiol. 275 (Endocrinol. Metab. 38):
E537-E542, 1988]. The former equations have been criticized and challenged by C. Des Rosiers, B. R. Landau, and H. Brunengraber [Am. J. Physiol. 259 (Endocrinol. Metab. 22):
E757-E762, 1990], and the latter recently by B. R. Landau,
J. Wahren, S. F. Previs, G. K. Ekberg, D. Yang, and H. Brunengraber
[Am. J. Physiol. 274 (Endocrinol. Metab. 37):
E954-E961, 1998]. Landau et al. claimed that our equations
were in error and "corrected" them. Their analysis, and their
values for recycling and gluconeogenesis (GNG) differ markedly from
ours. We show here our equations and estimates of recycling and GNG to
be correct. We present here a theoretical analysis of recycling and
discuss the determination of the Cori Cycle and GNG. We illustrate by
numerical examples the difference in parameters of glucose metabolism
calculated by the methods of Katz and Landau. J. Radziuk and W. N. P. Lee [Am. J. Physiol. 277 (Endocrinol Metab. 40):
E199-E207, 1999] and J. K. Kelleher [Am. J. Physiol. 277 (Endocrinol. Metab. 40):
E395-E400, 1999] present a mathematical analysis that,
although differing in some respects from Landau's, supports his
equation for GNG. We show in the
APPENDIX that their derivation of the
equation for GNG is incorrect.
glucose; mass isotopomer analysis
 |
THE SYSTEM |
We assume a steady state and, as in fasting, no formation of liver
glycogen from glucose. In mass isotopomer analysis with [U-13C]glucose, the
fractions (%) of labeled glucoses and lactate in blood are designated,
respectively, as "M" and
"m" values, with a subscript,
the index, indicating the number of
13C carbons per molecule. Thus
M0,
M1,
M2...M6
is glucose containing no, or 1, 2, 3...6 13C carbons per labeled molecule,
and m0,
m1,
m2,
m3 are lactate molecules and contain no, or up to 3 13C carbons. We designate the sum
of labeled molecules as
M or
m. Thus
We
also designate the product of the M or
m values with the index as
Mn or
mn. Thus
These
expressions show the number of 13C
carbons per 100 molecules of glucose or lactate.
In the numerical examples we assume net glucose production (replacement
of label by nonlabeled carbon) to be 2 mg · min
1 · kg
1.
There is a continuous infusion of 0.1 mg · min
1 · kg
1
of [U-1313C]glucose.
For simplicity, we neglect the mass of infused
[U-13C]glucose. We
also assume in some examples the direct conversion of pyruvate to
phosphoenolpyruvate (PEP), without
loss of 13C by exchange in the
operation of the tricarboxylic acid (TCA) cycle. As we show later, this
assumption does not affect the recycling of molecules.
 |
RECYCLING OF GLUCOSE MOLECULES AND OF GLUCOSE CARBON |
Lactate-pyruvate is the product of glycolysis and is also the major
precursor for gluconeogenesis (GNG). Thus there is always recycling of
glucose. This does not affect the net production of glucose but
increases the synthesis of glucose by liver in kidney, as will be
discussed in a later section.
As long as infusion of U-13C and
net glucose production are constant, the concentration of
[U-13C]glucose,
M6 containing six
13C carbons per molecule, will be
constant. In our example, glucose rate of appearance
(Ra) is also constant.
The
general expression is
An
identical value, 2 mg · min
1 · kg
1,
would be obtained with a nonrecycling tracer, such as
[3-3H]glucose.
In the resynthesis of glucose from dilute solutions of labeled lactate
(<5%), the statistical chance of recombining two labeled trioses is
very small and is neglected. The resynthesized glucose will contain
13C either in carbons 1, 2, 3 or
4, 5, 6 of glucose. If there were no recycling, the isotopomer spectrum
would be 5M6 + 95M0. In the
limit, at 100% recycling, the isotopomer spectrum will be 5M6 + 10M3 + 85M0. Thus, in
the limit, the concentration of labeled glucose will be one-third
M6 and two-thirds
M3, and the
concentration of labeled molecules will be trebled. The recycled
fraction will be
With
50% recycling the fraction of recycled molecules will be
and
for 10% recycling
Recycling will also increase the content of
13C carbons in glucose. Because
M3 contains three
13C carbons, and with the
assumption of direct conversion of pyruvate to PEP without loss of
13C, the fraction of recycled
carbon in the above example will be
at
100% recycling, and
at
10% recycling. However, although the exchange of
13C with
12C carbon does not affect the
recycling of molecules, as discussed below, it causes loss of
13C from recycled molecules.
In the conversion of pyruvate to PEP there occurs a loss of labeled
carbons by exchange with 12C. When
the flux of oxaloacetate (OAA) to citrate predominates, labeled
pyruvate containing three 13C
carbons will be converted to a mixture of
m3,
m2,
m1, and
m0. However, in
the fasted state the flux of OAA to PEP is much larger than the flux to
citrate (7). We show elsewhere (Katz and Tayek, unpublished) that, in
fasted humans, the predominant change is the conversion of
m3 to
m2, with little
loss of m2 and
negligible loss of
m1. Thus the sum
of m1 + m2 + m3 or
M1 + M2 + M3 changes little. This has also been accepted by Landau et al. (10) and the other
reviewers. Thus we have used
M3 in the above
example rather than the sum of recycled M values.
The general expression for the fraction of recycled molecules is
However,
in the conversion of pyruvate to PEP there is a loss of
13C carbons. The actual
13C content per molecule is shown
by the index, which indicates the number of
13C carbons for each
M and
m of glucose or lactate. Thus the
fraction of recycled carbon is
The
numerator represents the number of carbons in 100 molecules of recycled
glucose, and the denominator is the number in total glucose. We
illustrate in Table 1 our calculations for a 40-h-fasted man (6). The table also shows the average number of
13C carbons per molecule of PEP.
This is 2.07 13C carbons per
molecule. Thus, neglecting the recycling of lactate, ~29% of labeled
carbons of pyruvate were lost in its conversion of PEP.
We stress, in contradiction to Landau and co-workers (9, 10) and
Kelleher (8), the fact that the isotopomer spectrum provides for a
complete description, not only of the pattern of labeled molecules but
also of the labeled carbon. There is also equivalence in
"enrichment," the 13C
content of glucose, and relative specific activity obtained with
[U-14C]glucose. This
has been confirmed by experiment, by comparing the metabolism of
[U-13C]- and
[U-14C]glucose (7). We
have previously derived (13) and show in Table
2 the apparent
Ra if
[U-14C]glucose were
infused. Because of recycling, the specific activity of
[U-14C]glucose in
blood is increased, and apparent
Ra is decreased.
The recycling of carbon and the recycling of molecules are two
independent parameters of physiological interest, and we routinely report both in our studies. On the other hand, according to Landau et
al. (10), they are the same. We quote, "The fraction of glucose carbon recycled must be the same as the fraction of recycled molecules, contrary to Tayek and Katz."
 |
THE CORI CYCLE |
Cori pointed out the physiological role of recycling in maintaining
blood glucose well before the advent of isotopic tracers. Early
attempts to measure this recycling, named the Cori Cycle, were by
randomization of
[1-14C]- and
[6-14C]glucose. These
measure only the cycling of specifically labeled carbons. It is
apparent that Eq. 2, the recycling of
glucose molecules, equals the Cori Cycle. An essentially identical
expression was used previously by Kalderon et al. (4) to measure the
Cori Cycle in children. Thus the Cori Cycle equals Eq.
2
This
equation was challenged by Landau et al. (10). Following a previous
approach to recycling by Des Rosiers et al. (2), Landau introduced a
factor of 0.5; thus, according to these authors, the expression for
recycling is
They
designated this expression as the Cori Cycle. The reason, to quote
Landau, is "... the factor of 0.5 is required because only one-half
of triose units of mass
M1,
M2,
M3 are not
labeled and are not derived from
[U-13C]glucose. The
equations must represent the dilution only of the [U-13C]glucose
cycled..." We do not understand their rationale and completely
disagree. All the glucose molecules in blood, labeled and unlabeled,
are cycled to the same extent, and isotopic tracers represent the fate
of total glucose in blood. The reason that only one-half of
M1,
M2, and
M3 contain
13C is because of the use of
dilute solutions. If a 50% rather than a 5% solution of glucose were
used, one-half of the recycled molecules would contain
13C in both halves of the glucose.
Recycling would be the same as with the 5% dilution. Landau's
equation does not account for one-half of the recycled molecules and
one-half of the recycled carbon, and it vitiates the conservation of
mass. We believe Landau's "corrected" equation does not
represent any physiological parameter, and its designation as Cori
Cycle is unfortunate.
 |
GLUCONEOGENESIS |
In our previous studies (6, 13, 14), we derived an equation for GNG as
the product of the Cori Cycle and the dilution of glycolytic by
endogenous lactate. Landau et al. (10) accepted our approach, but their
estimates of both the Cori Cycle and dilution differ markedly from
ours. We present here an alternate direct approach and equation to
measure GNG. In a later section we discuss dilution and compare the new
expression and the calculated values of GNG with those derived by the
two methods. We show that the two methods are algebraically identical.
Glucose is formed by a condensation of two trioses. For
[14C]glucose the two
triose precursors are labeled, and the specific activity of
[14C]glucose is twice
that of the triose. The stoichiometry of glucose formation from a
diluted solution of
[U-13C]triose is
different. It is a condensation of one labeled and one unlabeled
triose. If the labeled triose is
m3, the
stoichiometry is
Thus
the 13C content of
m3 and
M3 is equal, with
three 13C carbons per molecule,
and the ratio
M3/m3
is 1 when GNG is 100%.
Consider the direct interconversion of
[U-13C]glucose and
lactate. Assume 100 micromoles (18 mg) of glucose containing 5%
[U-13C]glucose, or 30 microatoms of 13C converted to 200 micromoles of lactate, or to 10 m3 + 190 m0 molecules. As
required from the conservation of mass, the lactate will contain 30 microatoms of 13C. On further
interconversions, the steps are
Thus
m3 and
M3 will always
contain 30 microatoms of 13C. Mass
spectroscopy measures the fractions of mass of glucose or lactate containing 13C carbons. It does
not count molecules. The fraction of mass containing 1, 2, or 3 13C carbons from either lactate or
glucose remains the same. Both M3 and
m3 contain three
13C, and their fraction of mass in
the example of 13C is 30 13C carbons. This is not
affected by the conventional, arbitrary representation of
M and
m values as fractions (%) per 100.
In a dilute solution of glucose, the mixture of
M values results from a combination of
the corresponding m and
m0, with the 13C content of the
m and
M being equal. If 100% of glucose
production is by GNG
This
is supported by experiment (6). In 40-h-fasted human subjects, when
glycogen stores are depleted, the sum of
M1 + M2 + M3 is nearly the
same as the sum of
m1 + m2 + m3, the ratio is
close to 1, and GNG accounts for 80-100% of glucose production.
The corresponding equation for GNG derived by Landau et al. (10),
Kelleher (8), and Radziuk and Lee (11) is
differing
from our equation by a factor of 2. It implies the synthesis of
M values from two labeled precursors,
with a doubling of 13C content.
The calculation for GNG by this equation yields values that are too low
and physiologically untenable, that are in contradiction to
experimental finding, and that are exactly one-half of the correct
values obtained by us.
When there is production of glucose from hepatic glycogen, the value of
is
diluted, the ratio is <1, and
 |
DILUTION |
Labeled lactate-pyruvate in blood formed by glycolysis is diluted by
largely unlabeled lactate from amino acids and muscle glycogen. Landau
et al. (10) agree with Katz that GNG is the product of recycling and
dilution, but their values for recycling (the Cori Cycle) and dilution
differ greatly. Endogenous lactate formation will dilute the
concentration of labeled molecules and their
13C carbon content to exactly the
same extent. Thus both parameters can be used to calculate dilution,
and the results should be exactly the same. We estimated dilution by
comparing the content of 13C
carbon in glucose to that of lactate in blood. The dilution is
The numerator is the
13C content of glucose, and the
denominator is the 13C content of
blood lactate. The factor of 2 arises because the molecular weight of
13C glucose is twice that of
lactate. This expression is exactly equivalent to the ratios of
specific activities of
[14C]glucose and
[14C]lactate derived
from glucose. Gluconeogenesis is the product of recycling, the Cori
Cycle, and dilution, using dilution in terms of carbon, and we obtain
gluconeogenesis as Eq. 6. We compare in Table 2 the values
of GNG calculated by the equation
with
the equation of GNG as the product of the Cori Cycle, and dilution
using
the dilution obtained from 13C
carbon. The values for GNG are very similar, although the experimental
data used in the calculation are different. This supports our
assumptions, the validity of our analysis, and the expressions for the
Cori Cycle and dilution. The dilution in fasted humans ranged in the
great majority of subjects from 2- to 2.5-fold in the overnight fast, and from 2.5- to 3-fold in prolonged fasting. Thus GNG ranged from 2 to
3 times the rate of the Cori Cycle.
Landau et al. (10) estimated dilution from a comparison of the
concentration of labeled molecules in glucose and lactate. Their
results differ from those obtained with
13C carbon. Their expression for
dilution
is
The
rationale for the factor of 0.5 appears to be the same as in their
expression for the Cori Cycle. This expression neglects the fact that
200 molecules of lactate are formed from 100 molecules of glucose. The
error is apparent by considering the dilution of glycolytic lactate
derived from glucose by 100 moles of unlabeled lactate. According to
this equation, the dilution will be 50% rather than the correct
33.3%. The correct expression for dilution in terms of molecules is
Substituting this expression for dilution, in the equation
for GNG, as the product of Cori Cycle and dilution, we obtained the
expression for GNG
|
(Eq. 4)
|
We thus show that the apparently differing expressions for
GNG are algebraically identical. We stress that the expression for GNG,
was
derived solely from consideration of stoichiometry. It is independent
of calculations of the Cori Cycle, of recycling or dilution, or of any
assumptions on the pathways of gluconeogenesis. The algebraic identity
of the equations employing stoichiometry, the Cori Cycle, and the
different modes of dilutions establishes firmly the validity of our
assumptions and analysis.
 |
CO2 FIXATION |
The fixation of labeled CO2 in the
operation of the TCA cycle leads to the incorporation of label in the
carboxyl carbon of PEP. Because most of the pyruvate is unlabeled,
there will be a formation of
M1 and
m1, with
13C in the carboxyl carbon. The
extent of the fixation will depend on the labeling of the body
bicarbonate pool and the length of infusion, and in practice it will
not approach steady state. It will have a negligible effect on the
total 13C content of glucose but
may lead to a significant increase in fraction of recycled molecules.
We find in overnight-fasted humans that the fraction of
M1 is very low
(6) and the effect of CO2 fixation
negligible. However, in extensive recycling or prolonged infusion, the
M1 fraction may
equal and exceed
M3 (see Table 1).
In ionization in mass spectroscopy of lactate, the labile carboxyl is
partially split off, and spectra of intact lactate and its 2,3 carbon
moiety are obtained. This permits an estimate of M1 containing
13C in the carboxyl carbon and a
correction for
13CO2
fixation. At GNG values close to 100%, the overestimate in fasted
humans is of the order of 5-10%. In extensive cycling, as in
fasted young pigs (15), GNG is reduced by correcting for 13C fixation from an average of
104% to ~90%.
 |
ASSUMPTIONS |
In our studies with humans (6, 13, 14), the only assumption was that
lactate-pyruvate in blood is equilibrated with that in liver. Of
course, the concentration and specific activity or enrichment of
pyruvate in the liver cell will depend on numerous inflows and
outflows, labeled and unlabeled, into and from the TCA cycle
(acetyl-CoA, amino acids), and on the reactions of pyruvate kinase,
dehydrogenase, or carboxylase. We have shown perfect equilibration in
rats (7). Rats were infused with
[U-14C]- and
[U-13C]lactate and
alanine and lactate isolated from blood and liver tissue. The specific
activity, the enrichment of 13C,
and the isotopic pattern of lactate and alanine were virtually the same
and nearly identical in blood and liver. Such studies are impossible in
humans. Landau et al. (10) infused
U-13C in fasted humans and found
near equilibration of lactate and alanine in arterial but not in venous
blood. Alanine is formed from protein breakdown, and it is likely that
in a 5-h period steady state was not attained. The assumption of
complete equilibration of pyruvate in blood and liver is widely held in
the literature and appears to be shared by Kelleher (8) and Radziuk and
Lee (11).
Glycerol serves as an important substrate for glucose formation.
Glycerol entering gluconeogenesis at the triose-P stage will be
recycled just as glucose is. Indeed, Landau et al. (9) have shown that
glycerol carbons are randomized just as those of glucose. Thus the
formation of glucose from glycerol is included in our equations. This
is supported by the experiments of Sunehag et al. (12) with premature
babies, where glycerol was a major source of glucose.
In our analysis we have not considered the operation of cycling between
glucose and glycogen. As discussed by us previously (6), the operation
of such a cycle in the fasted state is controversial. Further studies
are required to resolve the issue and the question whether the
operation of such a cycle will affect our equations and our estimates
of Cori Cycle and GNG.
Our equations employ ratios such as
It
appears likely that a nonsteady state, incomplete equilibration, or
recycling with glycogen would affect in a similar manner the
M and
m values. The ratios and our equations
would hold under such conditions. Further studies are needed to test our equations under diverse conditions.
Landau et al. (10) faulted our analysis and calculations because, and
we quote, "...isotopic exchange was not adequately differentiated
from dilution, nor was condensation of labeled with unlabeled triose-P
properly equated." The claim is baseless. Indeed, it would be
difficult to maintain that any errors affecting metabolic pathways
would lead to equations differing exactly by the factor of two,
yielding one-half of our correct estimates. They claimed to support
their analysis and calculation by graphic models of glucose metabolism.
In their model they divided the glucose pool arbitrarily into two
subpools: a large one, as much as 80% "in brain, etc." that is
oxidized to CO2 and not recycled, and a small one, where recycling occurs. However, recycling affects the
whole body glucose pool. Isotopomer patterns taken from systemic blood
will be the same from whichever site the blood is sampled. It can be
readily shown that correct numerical calculations differ widely from
those shown by Landau et al. (10) for his models. The models are
untenable and provide no support for their equations.
 |
THE PHYSIOLOGICAL ROLE OF RECYCLING |
The net production of glucose, the replacement of glucose carbon by
unlabeled precursors, is not affected by recycling. In steady state,
the net production Ra can be
determined using nonrecycling tracers, such as
[3-3H]glucose from the
ratio of the rate of infusion and specific activity of glucose, or with
[U-13C]glucose, from
the ratio of the rate of infusion and
M6. If there were
no recycling, the concentration of
[U-13C]glucose would
equal M6.
However, as shown here, recycling increases the concentration of
labeled glucose molecules and the content of labeled carbon,
13C or
14C in blood glucose. In the
limit, at 100% recycling, the 13C
content of glucose or the specific activity of
[14C]glucose will be
doubled. Thus recycling increases the actual rate of glucose synthesis,
the output of glucose by liver and or kidney, or of GNG.
We have found in overnight-fasted humans the recycling of glucose, the
Cori Cycle, to be ~20 and 40% of glucose production contributed by
GNG and 60% by glycogenolysis. After a 40-h fast, Ra declined from ~2.2
mg · min
1 · kg
1
overnight to ~1.8
mg · min
1 · kg
1.
Recycling increased to 35-40%, and GNG contributed 85-100%
of glucose production. Thus the synthesis of glucose in the
overnight-fasted humans was increased by some 20%. In the 40-h fast,
the role of hepatic glycogen was negligible, and GNG, the production of
glucose, was increased by 30-35%. Thus recycling serves to
maintain the concentration of blood glucose and the size of the body
glucose pool, when net synthesis of glucose decreases. It is likely
that, without recycling, the 40-h-fasted subjects would be dangerously hypoglycemic.
 |
EXPERIMENTAL ASPECTS |
The criterion for the truth of a theory is agreement with experimental
data. We have in a recent publication (6) compared our estimates of GNG
in humans with values reported by other investigators, and the
agreement is close. Of special significance is the comparison with data
obtained by Landau and co-workers (1, 9) with glucose deuterated in
positions 2 and 5. This method is based on minimal
assumptions and is well validated. Both Landau and we find that %GNG
is ~40% after an overnight fast and 80-100% in prolonged
fasting. On the other hand, Landau's "corrected" equations show
20 and 40% for these conditions. Landau and co-workers acknowledge
that our values are much the same as those determined by his method,
but he persists in claiming that his equations are "theoretically
correct." They failed to realize that their "corrected" value
is one-half of the true value as calculated by us. They dismiss our
values as being accidental, a fluke.
The use of
[U-13C]glucose is
preferable to radioactive tracers for human studies. Calculations by
mass isotopomer analysis are simple. They provide much more information
about carbohydrate metabolism than can be attained by a combination of
several glucoses labeled with 14C
or 3H. The infused amount of
U-13C is small, approaching tracer
levels, and does not affect endogenous metabolism. The required blood
sample is small, as available in studies of neonatal babies. The
equipment is much cheaper than NMR and widely available. Kalderon et
al. (4) were the first to use mass isotopomer analysis in their studies
of children. We have used this approach for studies with fasted humans
(6), cancer patients (14), and diabetics (13), and Sunehag et al. (12)
employed it with premature babies kept on parenteral nutrition. Resolution of current disputes should lead to a wider application of
our analysis and equations.
 |
APPENDIX A |
Recycling in Glycogen Synthesis and GNG
The analysis of recycling in the present paper is an extension of that
used by Katz et al. (5) in the study of the indirect path of glycogen
synthesis. This was challenged by Des Rosiers, Landau, and Brunengraber
(2). With a dilute solution of
[U-13C]glucose,
one-half of the glycogen molecule formed in the indirect path is
unlabeled, just as in GNG. This led Des Rosiers et al. to introduce the
factor of 0.5 in their equation, just as in their equation for the Cori
Cycle. Accordingly, they calculated the contribution of the indirect
path to be ~35% rather than 50% according to Katz. They did not
distinguish the recycling of molecules from the recycling of carbon.
The error of Des Rosiers et al. was not realized at the time by Katz
and was not commented upon. A critique of Des Rosiers's rationale and
calculations would parallel closely the present critique of Landau et
al. and is not presented here.
 |
APPENDIX B |
Response to Kelleher, Radziuk, Lee, and Landau
Kelleher misunderstood our equations and misquotes them (see Table 1 of
Ref. 8). A statement in her abstract, "Landau's approach is based
on analyses of labeled molecules, while Tayek and Katz's is based on
labeling of carbon atoms..." is not correct, and this should be
apparent to readers of our review.
Kelleher does not consider recycling nor the equations of Landau et al.
She claims to derive the expression for GNG from binomial probability.
The binomial theorem serves to predict the frequency of the products as
a function of the concentration of precursors. It also serves, as used
by Hellerstein and Neese (3), to obtain the concentration of the
precursor from that of the products. The frequency depends solely on
the fractional concentration of the precursor. For example, with a 20%
solution of
[U-13C]lactate, the
direct conversion to glucose would yield
This
tells us nothing about recycling or GNG, which may range from 0 to
100%. To equate the equation for GNG with the term "2 ab" in the
expression (a + b)2 with GNG, and
use it to prove Landau's equation, is simplistic and incorrect.
Radziuk and Lee (11) offer, by employing an awkward, formal notation, a
review of tracer theory with 14C.
Most of it is well established and noncontroversial. They fail to
realize the distinction between
14C and
[U-13C]glucose. They
do not realize that
m3 and
M3 both contain
three 13C carbons. We quote,
"... a factor of 2 is again present, because two molecules of
lactate yield one of glucose, so that twice the fraction of glucose
molecules will be labeled relative to lactate molecules." True, but
only for 14C. We have dealt with
the fallacy of this statement, the cardinal error of Landau, in our review.
Our fundamental difference with the array of investigators disputing
our analysis is on the role of theory and experiment in research. They
admit that the equations of Landau and his supporters yield
physiologically untenable values. They fail to account for the
discrepancy. In accord with Landau, Kelleher quotes, "[a] correct
equation can yield incorrect answers." In our judgment, incorrect
answers, discrepancy between experiment and theory, discredit the
theory. We provide practical equations that provide solutions for
physiological parameters and that are admittedly valid. We believe that
the submission of theories in conflict with experiment is
irresponsible, and their publication unfortunate.
 |
ACKNOWLEDGEMENTS |
This study was supported by a National Institute of Diabetes and
Digestive and Kidney Diseases Clinical Investigator Award, K08-DK-02083
(to J. A. Tayek) and a Harbor-UCLA General Research Center Grant,
M01-RR-00425.
 |
FOOTNOTES |
Address for correspondence and reprint requests: J. Katz, 2509 Bombadil
Lane, Davis, CA 95616.
 |
REFERENCES |
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K. Ekberg,
W. C. Schumann,
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and
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1997[Medline].
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Des Rosiers, C.,
B. R. Landau,
and
H. Brunengraber.
Interpretation of isotopomer patterns in tracing glycogen synthesis and glucose recycling using [13C6]glucose.
Am. J. Physiol.
259 (Endocrinol. Metab. 22):
E757-E762,
1990[Abstract].
3.
Hellerstein, M. K.,
and
R. A. Neese.
Mass isotopomer distribution analysis, a technique for measuring biosynthesis and turnover of polymers.
Am. J. Physiol.
263 (Endocrinol. Metab. 26):
E988-E1001,
1992.
4.
Kalderon, B.,
S. H. Korman,
A. Gutman,
and
A. Lapidot.
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