Lactate release from adipose tissue and skeletal muscle in vivo: defective

insulin regulation in insulin-resistant obese women

Veronica Qvisth, Eva Hagstrom-Toft, Erik Moberg, Stefan Sjoberg, and Jan Bolinder
Department of Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm, Sweden
Submitted 7 March 2006; accepted in nal form 23 October 2006
Qvisth V, Hagstro m-Toft E, Moberg E, Sjo berg S, Bolinder
J. Lactate release from adipose tissue and skeletal muscle in vivo:
defective insulin regulation in insulin-resistant obese women. Am J
Physiol Endocrinol Metab 292: E709E714, 2007. First published
October 31, 2006; doi:10.1152/ajpendo.00104.2006.To study the local
tissue lactate production in the normal state and its possible distur-
bances in insulin resistance, rates of lactate release from adipose tissue
(AT) and skeletal muscle (SM) were compared postabsorptively and
during a hyperinsulinemic euglycemic clamp in 11 healthy nonobese
and 11 insulin-resistant obese women. A combination of microdialy-
sis, to measure interstitial lactate, and the
133
Xe clearance technique,
to determine local blood ow, were used. In the controls, local blood
ow increased by 40% in SM (P 0.05) and remained unchanged in
AT, whereas the interstitial-plasma difference in lactate doubled in
AT (P 0.005) and was unaffected in SM during hyperinsulinemia.
In the obese, blood ow and interstitial-plasma difference in lactate
remained unchanged in both tissues during hyperinsulinemia. The
lactate release (mol 100 g
1
min
1
) was 1.17 0.22 in SM and
0.43 0.11 in AT among the controls (P 0.01) and 0.86 0.23 in
SM and 0.83 0.25 in AT among the obese women in the postab-
sorptive state. During insulin infusion, lactate release in the controls
increased to 1.92 0.26 in SM (P 0.005) and to 1.14 0.22 in AT
(P 0.005) but remained unchanged in the obese women. It is
concluded that AT and SM are both signicant sources of lactate
release postabsorptively, and AT is at least as responsive to insulin as
SM. The ability to increase lactate release in response to insulin is
impaired in AT and SM in insulin-resistant obese women, involving
defective insulin regulation of both tissue lactate metabolism and local
blood ow.
microdialysis; blood ow
DISTURBANCES IN WHOLE BODY LACTATE TURNOVER appear to be of
importance in the development of insulin resistance. Elevated
fasting plasma levels of lactate have been reported in both
obese and type 2 diabetic subjects (29, 36). Moreover, in-
creased fasting plasma lactate is suggested to be an indepen-
dent risk factor for development of type 2 diabetes (45). It is
postulated that increased lactate levels in type 2 diabetes reect
the rate of Cori cycling of lactate, with accelerated hepatic
gluconeogenesis and elevated fasting glucose as a consequence
(9, 33).
Lactate is produced from glucose and glycogen through
glycolysis, by the conversion of pyruvate by lactate dehydro-
genase, in virtually all human organs and tissues. The produc-
tion of lactate is not only an anaerobic energy source and a
precursor for gluconeogenesis and glycogen synthesis in the
liver but also an energy substrate to compete with glucose for
aerobic oxidation in peripheral tissues (24). Furthermore, it is
suggested that there is an intracellular lactate shuttle where the
lactate produced directly within the cell is transported in the
mitochondria for oxidation (4).
Skeletal muscle is considered to be the major site of lactate
production. The regulation of lactate metabolism in muscle
during exercise is well studied, whereas lactate production at
rest is less well characterized. During exercise, the muscle
produces lactate to yield energy from anaerobic glycolysis;
however, there is also a signicant lactate production in the
fully oxygenated contracting muscle (40). Likewise, at rest,
skeletal muscle would seem to be an important tissue for
lactate production during insulin stimulation, since insulin-
mediated glucose uptake takes place mainly in the muscle.
However, in arteriovenous balance studies, only a small or no
net release from the limb was registered postabsorptively (12,
44), and no increase in lactate release was seen over the
forearm during hyperinsulinemia or after a meal (20, 35, 44).
Conversely, studies with lactate isotopes have demonstrated
that there is a continuous uptake and release of lactate in the
skeletal muscle (8, 40) and that the lactate release increases
during hyperinsulinemia (8, 32). Furthermore, studies using
microdialysis have shown higher lactate levels in skeletal
muscle than in plasma in the fasting state and that interstitial
lactate levels in muscle increase in response to oral glucose
ingestion (23) and hyperinsulinemia (17), indicating lactate
release.
Many studies, using different techniques, have shown that
adipose tissue is also a signicant source of lactate release (11,
14, 16, 22). The lactate release from adipose tissue is demon-
strated to increase in response to oral glucose ingestion (16, 19,
21) and hyperinsulinemia (11, 14, 17, 19).
In insulin-resistant conditions, the regulation of lactate pro-
duction from skeletal muscle and adipose tissue is poorly
elucidated. In skeletal muscle, studies using arteriovenous
balance and isotope techniques have registered both increased
and similar rates of skeletal muscle lactate release in type 2
diabetics compared with controls (1, 5, 9). In adipose tissue,
comparison of lactate release with microdialysis in lean and
obese men has shown impaired ability to increase lactate
production following oral glucose in obese subjects (21). In
contrast, rst-degree relatives of type 2 diabetics appear to
have increased lactate production from adipose tissue during
hyperinsulinemia (37).
Thus the regulation and possible disturbances in insulin-
resistant conditions of lactate production in human skeletal
muscle and adipose tissue at rest remain largely unknown. The
aims of the present study were, rst, to compare the basal rates
Address for reprint requests and other correspondence: V. Qvisth, Diabe-
tesmottagningen, Ersta Hospital, Box 4622, S-116 91 Stockholm, Sweden
(e-mail: veronica.qvisth@ki.se).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked advertisement
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Am J Physiol Endocrinol Metab 292: E709E714, 2007.
First published October 31, 2006; doi:10.1152/ajpendo.00104.2006.
0193-1849/07 $8.00 Copyright 2007 the American Physiological Society http://www.ajpendo.org E709
of lactate release in human adipose tissue and skeletal muscle
and, second, to evaluate the effects of insulin on lactate release
in these two tissues in both healthy normal-weight and in
insulin-resistant obese women. The effects of insulin were
studied during a hyperinsulinemic euglycemic clamp. The rates
of net lactate release in adipose tissue and skeletal muscle were
assessed by using the combination of microdialysis, to measure
interstitial lactate, and the
133
Xe clearance technique, to deter-
mine local blood ow.
MATERIALS AND METHODS
Subjects. The study was comprised of 11 nonobese [age 42 2 yr,
body mass index (BMI) 22.8 0.6 kg/m
2
] and 11 obese (age 37 1
yr, BMI 39.9 0.4 kg/m
2
) women. They were all healthy and did not
take any regular medication. The subjects gave their informed con-
sent, and the study was approved by the Ethics Committee of the
Karolinska Institute.
Microdialysis. The principle of microdialysis has been described in
detail previously (41). The microdialysis catheter (CMA/60; CMA
Microdialysis, Stockholm, Sweden) consists of a semipermeable
membrane (30 0.62 mm, molecular mass cutoff 20 kDa) connected
to the end of a double-lumen polyurethane tube. The probe was
inserted in the tissue and was continuously perfused using a precision
pump (CMA/100 microinjection pump; CMA Microdialysis) with a
sterile solution. An exchange of metabolites then takes place over the
microdialysis membrane, and the composition of the outow solution
reects the extracellular uid.
Study protocol. All subjects were investigated in the supine posi-
tion after an overnight fast. The experiment was started in the morning
(7:30 AM). Body composition (fat and lean body mass) was deter-
mined with bioelectrical impedance analysis, as previously described
(25). The validity of body fat measurements with this method has been
demonstrated by others to have good correlation with the reference
method (dual-energy X-ray absorptiometry; see Refs. 28 and 43).
A retrograde catheter (Venon) was inserted in a dorsal hand vein.
The hand was placed in an air-heated box (63C) for sampling of
arterialized venous plasma. After supercial skin anesthesia (EMLA;
Astra, Sodertalje, Sweden), microdialysis catheters were inserted in
the periumbilical abdominal subcutaneous adipose tissue and in the
medial part of the gastrocnemius muscle. The catheters were contin-
uously perfused with Ringer solution (Apoteksbolaget, Umea, Swe-
den) containing (in mmol/l) 147 Na, 4 K, 2.3 Ca, and 156 Cl at a ow
rate of 0.3 l/min. This ow rate has been shown to give almost
complete recovery (95%) of lactate in skeletal muscle and adipose
tissue (17).
After an equilibration period of 120 min, the dialysate samples
were collected in 30-min fractions for analysis of lactate. Plasma
samples were drawn in the middle of each dialysate fraction for
determination of lactate, glucose, and free insulin. After a 60-min
basal sampling, the subjects were given an insulin infusion (80 mU m
body surface area
2
min
1
; Actrapid; NovoNordisk) for 90 min.
Euglycemia was maintained by means of a variable glucose infusion
(200 mg/ml) and bedside glucose measurements (HemoCue, A

n-
gelholm, Sweden) every 5 min.
Blood ow measurements. The tissue blood ow was assessed with
the
133
Xe clearance technique, as described in detail previously (26).
Briey, in adipose tissue,
133
Xe (1.0 MBq in 0.1 ml saline; Mallinck-
rodt, Petten, The Netherlands) was injected percutaneously in the
paraumbilical subcutaneous tissue, opposite to the microdialysis cath-
eter, 30 min before the start of the baseline period. After 30 min of
equilibration, the clearance rate was monitored by a scintillation
detector (Mediscint; Oakeld Instruments, Oxford, UK) continuously
throughout the study periods. In skeletal muscle, the
133
Xe decay
curve becomes multiexponential over time, and the blood ow has to
be calculated from the initial monoexponential part of the
133
Xe
washout curve (38). Therefore, in the present studies,
133
Xe (0.3 MBq
in 0.1 ml saline) was injected two times in the medial part of the
contralateral gastrocnemius muscle. The rst injection was given after
25 min of basal sampling. The second injection was given after 55 min
of insulin infusion. Recordings were started 5 min after the injection
and continued for 30 min. The rst 10 min of the skeletal muscle
decay curve was used for calculations.
Adipose tissue and muscle blood ow was calculated according to
the following equation:
TBF k 100 (ml 100 g
1
min
1
)
where TBF denotes tissue blood ow, k denotes the rate constant of
the decay of the residual activity, and the tissue-to-blood partition
coefcient. The values for were set at 10 ml/g for adipose tissue and
0.7 ml/g for muscle (26, 27).
The reproducibility of the
133
Xe clearance technique has previously
been evaluated in methodological experiments. The coefcient of
variation for duplicate measurements of basal blood ow in skeletal
muscle was 20.6% when the blood ow was measured in the same
subject with 410 mo between the measurements. Based on this
nding, it was calculated that, in 10 subjects, a difference of blood
ow of 0.4 ml 100 g
1
min
1
, i.e., 23% of the blood ow at basal
conditions, could be detected with 80% power at the 5% signicance
level (32).
Calculations. The absolute rates of lactate release from adipose
tissue and skeletal muscle were calculated according to Ficks prin-
ciple:
(V A) Q (1 hematocrit 10
2
) (mol 100 g
1
min
1
)
where V denotes venous lactate, A arterial lactate, and Q calculated
plasma blood ow.
Conversion of interstitial (I) to venous (V) lactate concentrations
was made according to the following equation:
V (I A) (1 e
PS/Q
)
where PS is the permeability surface product area (adopted to be
4 ml 100 g
1
min
1
for lactate; see Ref. 13).
Biochemical analysis. Microdialysate lactate was determined with
an enzymatic uorometric method, using a tissue sample analyzer
(CMA/600; CMA Microdialysis). In agreement with earlier ndings,
the coefcient of variation for duplicate analyses of lactate during the
basal period was 6.1 0.1% in skeletal muscle and 6.0 0.1% in
adipose tissue. Plasma lactate was determined by an enzymatic ouro-
metric method (34). Plasma free insulin was determined by a com-
mercial RIA (Pharmacia, Uppsala, Sweden). Plasma glucose was
analyzed using the hospitals routine clinical laboratory.
Statistics. The results are expressed as means SE. Statistical
analyses were performed with repeated-measures ANOVA followed
by post hoc analyses with Fischers protected least-signicant differ-
ence test. Because of nonhomogenous correlations, a general linear
model for mixed effects was used when the interstitial-arterial differ-
ence lactate values were compared. Students paired t-test was used
for the comparison of fasting glucose between the study groups. A
value of P 0.05 was considered statistically signicant. A statistical
software package (StatisticaVersion 7.1 for personal computer; Stat-
soft) was used for all statistical calculations.
RESULTS
The total body fat masses were 67.4 1.3 kg for the obese
women and 20.4 1.8 kg for the nonobese women (P
0.001). The corresponding lean body masses were 43.1 0.7
and 46.3 1.5 kg (not signicant).
Plasma glucose, lactate, insulin, insulin sensitivity [metab-
olized glucose per unit of insulin (M/I) ratio], and local blood
E710 LACTATE RELEASE IN ADIPOSE TISSUE AND SKELETAL MUSCLE
AJP-Endocrinol Metab VOL 292 MARCH 2007 www.ajpendo.org
ow rates and fractional release of lactate in adipose tissue and
skeletal muscle are presented in Table 1.
Basal conditions. In the fasting state, plasma glucose and
lactate did not differ between the obese and nonobese women.
In contrast, fasting plasma insulin levels were 2.5 times higher
in the obese women than in the nonobese women, implying
insulin resistance (P 0.001).
The fractional release of lactate from adipose tissue and
skeletal muscle was calculated as the difference between the
interstitial lactate concentration in the two respective tissues
and the arterialized venous plasma lactate level. The intersti-
tial-plasma difference in lactate was 3.5 times higher in
skeletal muscle compared with adipose tissue postabsorptively
in the lean women (P 0.001, mixed model) and about two
times as high in the obese women (P 0.001, mixed model).
The basal interstitial-plasma lactate difference in adipose tissue
was signicantly higher in the obese women compared with the
nonobese women (P 0.05, mixed model), whereas in skeletal
muscle it did not differ between the study groups.
There were no signicant differences in blood ow rates
between the controls and the obese women in the fasting state
in either adipose tissue or skeletal muscle. Basal blood ow
rates in adipose tissue were higher than in skeletal muscle in
both the controls and obese subjects (P 0.05).
The rates of lactate release in adipose tissue and skeletal
muscle are shown in Fig. 1. Ficks principle for calculation of
lactate release is applicable only during steady-state condi-
tions. The lactate release from adipose tissue and skeletal
muscle was calculated from the last 30-min steady-state peri-
ods at baseline and during the insulin infusion. There were no
signicant changes in blood ow, plasma, and interstitial
lactate during these periods (ANOVA, repeated measure-
ments). In the controls in the postabsorptive state, the rate of
lactate release in skeletal muscle was three times higher than in
adipose tissue (P 0.01). However, there were no signicant
differences in basal lactate release between the two tissues in
the obese women. The rates of lactate release at baseline did
not differ between the study groups in either adipose tissue or
skeletal muscle.
Effect of insulin. The insulin sensitivity during the clamps
was signicantly lower in the obese women than in the nono-
bese women (P 0.001). This conrms insulin resistance in
the obese women. The plasma lactate levels increased in
response to insulin, and this rise was more pronounced among
the lean women compared with the obese women (P 0.005).
The interstitial-plasma difference in lactate increased in
adipose tissue and remained unchanged in skeletal muscle in
the lean subjects during hyperinsulinemia (P 0.005, mixed
model). However, in the obese subjects, no signicant changes
in the fractional release of lactate from either adipose tissue or
skeletal muscle were seen in response to insulin. There were no
differences in the fractional release of lactate from adipose
tissue and skeletal muscle between the study groups during the
insulin infusion.
The local blood ow rates among the lean women increased
in skeletal muscle (P 0.05) and remained unchanged in
adipose tissue in response to intravenous insulin. In the obese
women, however, the blood ow rates remained unchanged in
both adipose tissue and skeletal muscle during the insulin
infusion.
The rates of lactate release during insulin infusion increased
by about one-half in skeletal muscle and doubled in adipose
tissue in the control women (P 0.005). No changes in lactate
release from either skeletal muscle or adipose tissue were seen
in the obese women during the insulin infusion (Fig. 1).
DISCUSSION
In the present study, the rates of lactate release from both
adipose tissue and skeletal muscle have for the rst time been
compared in healthy nonobese subjects and in insulin-resistant
obese subjects in vivo.
In corroboration with previous studies in healthy subjects,
we found that both skeletal muscle and adipose tissue are
signicant sources of lactate production in the postabsorptive
state and that insulin stimulates net lactate release in both
tissues (1, 5, 11, 14, 16, 17, 19, 2123). The basal lactate
release was, as expected, higher in skeletal muscle than in
adipose tissue. However, in response to insulin infusion, the
relative increase in net lactate release was clearly more pro-
nounced in adipose tissue compared with muscle tissue. This is
in keeping with previous ndings indicating that plasma lactate
is mainly determined by the rate of glucose disposal in extra-
muscular tissues such as adipose tissue rather than skeletal
muscle during hyperinsulinemia (44).
By contrast, our results showed impaired insulin-stimulated
lactate release in both skeletal muscle and adipose tissue in the
insulin-resistant obese women. This is in accordance with
previous data where the rates of lactate release from adipose
tissue increased in lean but not in obese subjects following an
Table 1. Glucose, insulin, and lactate concentrations in P,
M/I ratio, I-A difference, and lactate and blood ow rates in
skeletal muscle during basal state and insulin infusion in
obese and nonobese subjects
Subjects P Level
(lean vs.
obese) Lean Obese
fP glucose, mmol/l 4.90.1 5.20.1 NS
P insulin, pmol/l
Basal 38.52.3 97.413.5 0.001
iv Insulin 763.137.7* 1,000.369.3* 0.05
P lactate, mmol/l
Basal 0.540.05 0.530.01 NS
iv Insulin 1.290.06* 0.990.02* 0.005
M/I ratio, mg kg LBM
1

min
1
to pmol/l 0.0110.001 0.0040.001 0.001
I-A difference lactate, mmol/l
Adipose tissue
Basal 0.390.11 0.980.24 0.05
iv Insulin 0.880.18* 0.860.12 NS
Skeletal muscle
Basal 1.310.20 1.790.19 NS
iv Insulin 1.550.18 1.570.19 NS
Blood ow rates, ml 100
g
1
min
1
Adipose tissue
Basal 2.780.41 1.800.29 NS
iv Insulin 2.740.20 2.120.31 NS
Skeletal muscle
Basal 1.590.20 1.050.29 NS
iv Insulin 2.560.31* 1.090.27 0.05
Values are means SE. *P 0.05, basal vs. insulin-stimulated samples
within the tissue. NS, nonsignicant; fP, fasting plasma; P, plasma; M/I,
metabolized glucose per unit of serum insulin; I-A, interstitial-arterial.
E711 LACTATE RELEASE IN ADIPOSE TISSUE AND SKELETAL MUSCLE
AJP-Endocrinol Metab VOL 292 MARCH 2007 www.ajpendo.org
oral glucose load (21). It is well known that there are regional
differences in the intermediate metabolism, both in various fat
deposits and skeletal muscles. We believe this is important to
take into consideration in the context of extrapolating data
from a local fat deposit or skeletal muscle to the whole body.
However, our ndings may suggest that, when muscle and
adipose tissue masses are considered, the adipose tissue in the
obese subjects probably is much more important than skeletal
muscle for the total rate of lactate release at least postabsorp-
tively because of the pronounced increase in total fat mass (in
this study 47 kg). This may imply that the increased adipose
tissue mass in obesity is the main contributor to the enhanced
lactate turnover and gluconeogenesis seen in type 2 diabetes in
the postabsorptive state (9).
Contradictory, in this study, the concentrations of fasting
plasma lactate did not differ between the controls and obese
women. Increased levels of fasting plasma lactate have previ-
ously been registered in both type 2 diabetes (1, 36) and
obesity (21). However, Lovejoy et al. (29) found no difference
in basal plasma lactate between obese and lean subjects,
whereas a negative correlation between basal plasma lactate
and the degree of insulin sensitivity was demonstrated. Fur-
thermore, it is well known that it is the visceral fat deposits that
are associated with insulin resistance and type 2 diabetes.
Consequently, it could be increased lactate release from intra-
abdominal fat masses via the portal system, which do not reach
the systemic circulation that contributes to glucose production
in the liver. This is supported by earlier studies with isolated
adipocytes in vitro that showed higher lactate production in
visceral fat cells than in subcutaneous cells (31).
The impaired net lactate release from skeletal muscle and
adipose tissue in response to insulin may explain the lower
plasma lactate levels that were seen in the obese women during
hyperinsulinemia in the present study, as well as in earlier
investigations of obesity (28) and type 2 diabetics (39).
Our ndings with local blood ow rates in the control group
are consistent with previous studies showing that insulin stim-
ulates the local blood ow in skeletal muscle (2, 6) probably
via insulin-mediated capillary recruitment (38). In adipose
tissue, the blood ow remained unchanged, and earlier studies
have shown both stimulation and no effect by insulin on the
nutritive blood ow in adipose tissue (17, 32). The fractional
release of lactate, on the other hand, increased only in adipose
tissue during insulin infusion. This may suggest that the stim-
ulatory effect of insulin on net lactate release in skeletal muscle
was mainly the result of an insulin-induced increase in blood
ow rates, whereas in adipose tissue insulin predominantly
stimulates the production of lactate.
However, given the coefcient of variance of the
133
Xe-
clearance washout technique, detecting small differences in the
calculated lactate release may be difcult.
Nevertheless, the diminished rise in lactate release from
skeletal muscle seen in the obese women may, at least to some
extent, have been a result of the impaired blood ow response
to insulin and may indicate an association between obesity and
defective blood ow regulation in adipose tissue and skeletal
muscle. Accordingly, an impaired ability of insulin to increase
skeletal muscle blood ow has previously been reported in
states of insulin resistance, and it has been suggested that
diminished tissue perfusion could contribute to insulin resis-
tance (3, 6).
When estimating the lactate release, we used the same PS
value (4 ml 100 g
1
min
1
) in all calculations, as previously
suggested (13). The PS value, the product of permeability and
surface area, is considered to be comparable in skeletal muscle
and adipose tissue (13). However, recent studies have indicated
that the calculated PS value for various substances may differ
between lean and insulin-resistant obese subjects. Coppack et
al. (10) found that the PS value for glycerol in subcutaneous
abdominal adipose tissue declined with increasing adiposity.
Likewise, Gudbjornsdottir et al. (15) have demonstrated re-
duced PS values for glucose and insulin in skeletal muscle in
insulin-resistant type 2 diabetic subjects. In both studies, the PS
values in the obese subjects were approximately one-half that
of the controls. To evaluate to what extent reduced PS values
in the obese subjects would inuence the results in the present
study, we recalculated our data with the PS value set to
2 ml 100 g
1
min
1
for the obese subjects. The rates of lactate
release from adipose tissue and skeletal muscle then declined
Fig. 1. Effect of insulin infusion on the rates of
lactate release in adipose tissue and skeletal muscle
in 11 nonobese and 11 obese subjects. Values are
means SE. *P 0.05 for differences between the
basal and hyperinsulinemic period; P 0.05 for
differences between the nonobese and obese sub-
jects.
E712 LACTATE RELEASE IN ADIPOSE TISSUE AND SKELETAL MUSCLE
AJP-Endocrinol Metab VOL 292 MARCH 2007 www.ajpendo.org
by 1020% in these obese subjects; however, the comparison
between lean and obese subjects did not change.
In the present study, the true lactate production in skeletal
muscle may have been underestimated because of simulta-
neous lactate uptake (8, 40). In adipose tissue, on the other
hand, lactate uptake has not been shown. However, our main
aim was to study the net lactate release, and the relative
contributions, of adipose tissue and skeletal muscle to whole
body lactate turnover in lean and obese subjects, since the net
tissue outow of lactate is probably most important in the
development of insulin resistance by delivery of lactate for
gluconeogenesis and glycogen formation in the liver.
Lactate production in skeletal muscle is traditionally consid-
ered to be higher in glycolytic type 2 bers than in oxidative
type 1 bers (42). In the present study, the gastrocnemius
muscle was investigated, which has a high proportion of
oxidative type 1 bers (18). Hence, the rates of lactate release
in other more glycolytic muscle groups may differ from our
results.
In summary, this study conrmed that adipose tissue is a
signicant source of lactate release in both the postabsorptive
state and during hyperinsulinemia. Insulin-resistant obese sub-
jects show an impaired ability to increase lactate release in
response to insulin in tissues involved in both blood ow and
tissue production. Because of the increased fat mass in obesity,
lactate release from adipose tissue would seem to be of greater
importance than lactate release from skeletal muscle and could
possibly contribute to the increased lactate turnover seen in
insulin resistance and type 2 diabetes.
ACKNOWLEDGMENTS
We acknowledge the excellent technical assistance of B.-M. Leijonhufvud,
K. Hertel, E. Sjolin, and K. Wahlen.
GRANTS
This study was supported by grants from the Swedish Research Council, the
Swedish Diabetes Association, the Karolinska Institute, and Stockholm
County.
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