Effects of High Sucrose or Starch-bran
on Glucose and Lipid Metabolism of
Normal and Diabetic Rats
Diets
WEN-JU LIN ANDJAMES W. ANDERSON
Medical Service, Veterans Administration Hospital, and
Department of Medicine, University of Kentucky College
of Medicine, Lexington, Ky. 40507
High carbohydrate diets containing 75%
to 85% of energy as carbohydrate are accompanied by a slight improvement of glucose metabolism of normal men (1, 2) and
by a significant improvement in glucose
metabolism of diabetic individuals (3-5).
However, when high carbohydrate diets are
fed to rats, some groups have reported improvement in glucose metabolism (6, 7)
whereas other groups have reported deterioration of the glucose tolerance (8).
High carbohydrate diets are accompanied
by higher tissue activities for glycolytic
enzymes in man (9) and in rats (10-12)
than values obtained with low carbohydrate
diets. Plasma insulin responses after oral
glucose are lower in men fed high carbohydrate diets than responses when conven-
tional diets are fed (1, 2). These observations (1, 2) have suggested that high carbohydrate diets are accompanied by an
enhanced sensitivity of tissues to insulin,
However, the mechanisms for alteration in
the glucose metabolism when high carbohydrate diets are fed remains unclear,
Hypertriglyceridemia frequently has been
reported when men or rats are fed high
carbohydrate diets. When normal men or
diabetic patients are fed formula diets containing sucrose, glucose or dextrin, increases in serum triglycéride values are
observed with regularity (13-15). Similar
observations have been made when rats
are fed diets containing large amounts of
Receivedfor publicationJuly 12, me.
584
Downloaded from jn.nutrition.org by guest on May 20, 2013
ABSTRACT
Normal and streptozotocin-diabetic
rats were fed a low
carbohydrate diet or one of two high carbohydrate diets (sucrose or
starch-bran). High carbohydrate diets were associated with slightly higher
plasma glucose levels in both control and diabetic rats. However, glucose
tolerance tests were not altered by the diets in either the control or diabetic
rats. Plasma and liver triglycéridevalues for control and diabetic rats fed
the high sucrose diet were similar to those of rats fed the low carbohydrate
diet. The starch-bran diet was associated with lower plasma and liver tri
glycéridevalues in both control and diabetic rats. Plasma triglycéride
values of diabetic rats fed the high sucrose diet or the low carbohydrate
diet were significantly higher than values of control rats fed the same diets.
On the other hand, plasma triglycéridevalues of diabetic rats fed the
starch-bran diet were similar to values for control rats fed the same diet.
These studies suggest that a high carbohydrate diet containing starch and
wheat bran is associated with a reduction in plasma triglycéridevalues in
both normal and diabetic rats. Liver glycolytic enzyme activities were sig
nificantly lower in diabetic rats than in control rats in all three dietary
groups.
J. Nutr. 107: 584-595, 1977.
INDEXING KEY WORDS
sucrose
• starch-wheat bran
• tri
glycéride •diabetes
585
LIPID METABOLISM AND HIGH CARBOHYDRATE DIETS
MATERIALS AND METHODS
Animals. Male Sprague-Dawley
rats
(150-170 g) 1 were housed in individual
TABLE 1
Composition of the diets
Low
carbohydrate
High
sucrose
Starchbran1
totalSucroseStarchBran1Protein,
Carbohydrate,
totalCaseinBran1Vegetable
oilDietary
totalCelluloseBran1Salt
fiber,
mixture8Vitamin
mixture*g/100g3232——4046—1266—4g/100g7272——1818—6—
1Starch-bran diet contained 20% of wheat bran
which had protein 10%, fat 3%, CHO 57% (values
were from Watt, B. K. & Merrill, A. L., composition
of Foods USDA Handbook No. 8, 1963) and dietary
fiber 30% (unpublished observations). Therefore,
this 20% wheat bran provided 12% carbohydrate,
2% protein and 6% dietary fiber.
2Salt mixture
(ICÑ Nutritional Biochemicals, Cleveland, Ohio)
contains: Sodium chloride, 13.93%; potassium biphosphate 38.91%; magnesium sulfate (anhydrous)
5.73%; calcium carbonate 38.14%; ferrous sulfate
2.70%, manganese sulfate 0.4%; potassium iodide
0.079% ; zinc sulfate 0.055% ; cupric sulfate 0.048%.
3Vitamin mixture (ICN Nutritional Biochemicals,
Cleveland, Ohio) contains (g/46 kg): Vitamin A
concentrate (200,00 u/g), 4.5; Vitamin D concen
trate (400,000 u/g), 0.25; a tocopherol, 5.0; ascorbic
acid, 45.0; inositol, 5.0; cholme chloride, 75.0;
menadione, 2.25; p-aminobenzoic acid, 5.0; niacin,
4.5; riboflavin, 1.0; pyridoxine hydrochloride, 1.0;
thiamin hydrochloride, 1.0; calcium pantothenate,
3.0; biotin, 0.02; folie acid, 0.09; vitamin B-12,
0.00135.
cages with a raised mesh floor. The rats
were fed a commercial stock diet2 for at
least 2 weeks before changing their diet.
All diets and water were fed ad libitum.
Diabetes was produced by the intravenous
injection of streptozotocin after a 16 to 20
hour fast. At the time of streptozotocin in
jection, the weight of the injected rats
matched that of the control rats. Diabetic
rats in group 1 received 50 mg streptozotocin/kg body weight. Plasma glucose
values and body weight were measured in
these rats in the nonfasted state at 15 to 21
days after streptozotocin injection. Diabetic
1HarÃ-an Industries, Cumberland, Indiana.
*Purina Laboratory Chow, Ralston Purina Co., St.
Louis, Missouri.
Downloaded from jn.nutrition.org by guest on May 20, 2013
sucrose or fructose (13, 16-19). Other
studies have suggested that when diabetic
patients are fed high carbohydrate diets
composed of solid foods with generous
amounts of starch and limited amounts of
oligosaccharides, an increase in serum tri
glycéridevalues does not occur (3, 20-22).
Recent studies (3) have suggested that the
introduction of wheat bran into the diet
protects diabetic patients from the devel
opment of hypertriglyceridemia when they
are fed 75% carbohydrate diets. Thus cer
tain high carbohydrate diets are accom
panied by hypertriglyceridemia
whereas
other diets may not produce an increase in
serum triglycéridevalues.
The primary objective of these experi
ments was to determine if high carbo
hydrate diets have different effects on the
glucose metabolism of diabetic rats com
pared to the effects observed in normal
rats. Whereas high carbohydrate diets have
beneficial effects on the glucose metabolism
of certain human diabetic patients (3-5),
we observed no significant differences in
the glucose metabolism of normal or dia
betic rats fed high carbohydrate diets com
pared with normal or diabetic rats fed low
carbohydrate diets. The secondary objec
tive of these experiments was to determine
if different types of high carbohydrate diets
have differing effects on lipid metabolism
of normal and diabetic rats. For this com
parison, we selected two different high
carbohydrate diets which we anticipated
would be accompanied by differences in
lipid metabolism. The high sucrose diet
was selected because previous studies (13,
17-19) suggested that this diet would be
accompanied by the greatest increases in
serum triglycéridevalues. The second high
carbohydrate diet was designed, on the
basis of previous observations (3), to pro
duce the minimum change in serum tri
glycéridevalues. Thus, the second high
carbohydrate diet did not contain sucrose
and the carbohydrate was provided by
starch and wheat bran. These studies indi
cate that the composition of high carbo
hydrate diets has a significant influence on
the response of serum triglycérides.
586
WEN-JU LIN AND JAMES W. ANDERSON
blotted dry. Mucosa was obtained by
scraping the intestine with a glass slide.
One portion of liver and the distal portion
of jejunal mucosa were homogenized in 20
volumes of a buffer containing 50
Tris, 100 HIM KC1, 1 mM EDTA, 5 mM
mercaptoethanol and 5 mM MgCl2 at pH
7.4. The homogenates were centrifuged at
105,000 x g for 60 minutes in a ultracentrifuge.3 The 105,000 X g liver supernatant
fraction was used for glucokinase (ATP:
D-glucose-6-phosphotransferase, EC 2.7.1.2),
glucose-6-phosphate (G-6-P) dehydrogenase ( D-glucose-6-phosphate :NADP oxidoreductase, EC 1.1.1.49) and malic enzyme
(L( —)-malate: NADP oxidoreductase (decarboxylating), EC 1.1.1.40) assays. Hexokinase
( ATP :D-hexose-6-phosphotransf er
ase, EC 2.7.1.1) assays were performed on
jejunal homogenates, and assays for hexokinase, G-6-P dehydrogenase and malic en
zyme were obtained on supernatant frac
tions. The other portions of liver and
jejunal mucosa were homogenized in 20
volumes of a buffer containing 20 mM
TES (N-tris[hydroxymethyl]methyl-2-aminoethone sulfonic acid), 10 mM MgSO4, 1
mM dithiotreitol and 100 mM sucrose at
pH 7.4 and centrifuged in a similar fashion.
The 105,000 X g supernatants were used
for pyruvate kinase (ATP:pyruvate phosphotransferase, EC 2.7.1.40) assays. All tis
sue preparation and weighing were carried
out at 4°.
Enzyme assays. Enzymes were assayed
at 28°in a recording spectrophotometer.*
Hepatic glucokinase and jejunal hexokinase
were assayed by the method of Vinuela et
al. (23) using 0.1 M glucose for liver and
10 mM glucose for jejunal mucosa (12).
Pyruvate kinase was measured by the
method of Bucher and Pfleiderer (24),
G-6-P dehydrogenase was measured by the
method of Langdon (25) and the method
of Ochoa (26) was used for malic enzyme
assays. Protein concentrations
in liver
supernatants, jejunal supernatants and ho
mogenates were measured by the method
of Lowry et al. (27). Bovine serum albu
min dissolved in the homogenizing buffer
used for the original sample, was used as a
standard. Enzyme activities were expressed
as /tmoles/minute/g tissue.
Glucose and glycogen measurements.
Plasma glucose estimations were performed
in duplicate
by the glucose oxidase
"Beckman
«
Beckman
Model L5-40, Fullerton, California.
Model 25, Fullerton, California.
Downloaded from jn.nutrition.org by guest on May 20, 2013
rats in group 2 received 35 mg streptozotocin/kg body weight. Plasma glucose
and body weight were measured in these
rats after a 4 hour fast, 15 to 21 days after
streptozotocin injection. This experiment
used a randomized blocks design. Diabetic
rats were divided into twelve blocks, three
rats in each, by matching both plasma glu
cose level and body weight. Control rats
were divided into nine blocks, again with
three rats in each by matching body
weight. Each of the three rats in a block of
control or diabetic rats were randomly as
signed to one of three experimental diets
( table 1 ). One diet was a low carbohydrate
diet and two diets were high carbohydrate
diets, the high sucrose and the starch-bran
diet. Preliminary studies of control rats in
dicated that the responses of glycolytic
and pentose phosphate pathway enzymes
in liver and jejunum to these experimental
diets were maximal at 10 days and re
mained in the same range for up to 32 days.
All rats in group 1 were given the diets on
the same day and were killed 14 to 32 days
(average of 25 days) later. Rats in group
2 were killed after being fed the diets for
21 days. The results for control rats in
groups 1 and 2 were similar and were com
bined for analyses.
Terminal plasma glucose values were
obtained from tail vein blood 1 day before
and the day of killing of nonfasted rats in
group 1. In group 2, between 1 and 5 days
before killing, the terminal plasma glucose
value was obtained from rats fasted for 4
hours. All rats were killed between 0800
and 1000 hours. On the day of killing, rats
were anesthetized with ether, and blood
was withdrawn by cardiac puncture. Blood
was centrifuged for 30 minutes at 1,600 X g
and 4°;plasma was removed and stored
in a freezer at —20°
until analysis.
Tissue preparations. After the rats were
killed, the abdomen was opened and two
portions of liver removed. Two segments of
jejunum located from 12 to 25 cm and from
25 to 45 cm beyond the pylorus were re
moved, slit longitudinally, washed free of
contents with distilled water at 4° and
587
LIPID METABOLISM AND HIGH CARBOHYDRATE DIETS
RESULTS
Plasma glucose values. Terminal plasma
glucose values in control rats fed high su
crose or starch-bran were slightly but not
significantly higher than values for the rats
fed the low carbohydrate
diet. Initial
plasma glucose values were similar for all
three groups of diabetic rats before the
test diets were initiated (table 2). Diabetic
rats in group 1 fed high sucrose or starchbran diets had significantly higher terminal
plasma glucose values than the rats fed
the low carbohydrate diet. Terminal plasma
glucose values for all diabetic rats in group
2 fed the high sucrose diet (441 ±180
mg/100 ml, mean ±so) or the starch-bran
diet (483 ±149) were slightly but not sig
nificantly higher than values for the low
carbohydrate group (411 ±142). There
were no significant differences between the
plasma glucose values of rats fed the highsucrose diet or the starch-bran diet. These
observations are similar to those of Baker
et al. (32).
Glucose tolerance tests were performed
on streptozotocin-injected rats with plasma
glucose values less than 300 mg/100 ml;
2 g glucose/kg body weight (33) was in
jected intraperitoneally after a 4-hour fast.
Glucose tolerance tests were also per
formed on four control rats from each dis Glucose Analyzer,
Beckman
Instruments,
Inc.,
Fullerton,
California.
»
Sigma Chemical Company, St. Louis, Missouri.
7 Dade Manual, Dade Division, American Hospital
Supply Corporation,
Miami, Florida.
TABLE 2
Plasma glucose in control and diabetic rats
Diabetic
2TerminalMild1
1Diet
Group
Control
mg/100 ml
Initial
TerminalGroup Initial
mg/100 ml mg/100 ml
mg/100 ml
mg/100
ml
Moderate2
Severe3
mg/100
ml
mg/100
ml
(9)4±12175 (12)±43446
(12)±48679" (12)±120375(3)±14218
(4)±
(5)±44—427
9569
(11)±43645"
(7)±36580
sucroseStarch-bran162(9)±22180 (12)±96444
(12)±123371(4)±36248
carbohydrateHigh
Low
(12)±71375 (12)±113187(2)±78450(2)±11530
(6)±64
(9)±34444 (12)±59514°
1Mild diabetes with mean plasma glucose levels less than 300 mg/100 ml. *Moderate diabetes with
mean plasma glucose level between 300 to 500 mg/100 ml. *Severe diabetes with mean plasma glucose
level above 500 mg/100 ml. «
Mean ±so with the number of rats in parenthesis. Means in the same verti
cal column with different superscript letters differ significantly (P < 0.05).
Downloaded from jn.nutrition.org by guest on May 20, 2013
method.5 Liver glycogen was measured as
described previously (28). Rabbit liver
glycogen 6 was used as a standard.
Total lipid and triglycéride measure
ments. The total lipid in liver was extracted
by homogenizing the tissue with a 2:1
(v/v) chloroform-methanol
mixture and
washing the filtered extract with one-fifth
volume of 0.9% NaCl (29). The resulting
mixture separated into two phases. The
lower chloroform layer contained the total
lipid extract. The weight of total lipid in
the chloroform layer was measured by the
gravimetric method. A measured aliquot
of the chloroform layer was used for tri
glycéridedeterminations. Liver triglycér
ide was estimated colorimetrically by the
Dade method.7 Serum triglycéride was
measured by the method of Levy (30) with
triolein in isopropanol as the standard.
Statistical analysis. Data were analyzed
by using the method of randomized block
design (31). When statistical significance
was found, Duncan's Multiple Range Test
(31) was applied to determine which mean
values were significantly different.
WEN-JU
588
LIN AND JAMES W. ANDERSON
TABLE 3
Body weight and weight changes in control and diabetic rats
Diabetic
Group 2'
Diets
Low carbohydrate
High sucrose
Starch-brana494
Controla1
Group I1
±60(+109)«
466 ±40(+100)
482 ±76(+100)a338
Mild
±35(+43°)
320 ±53(+16»)
303 ±38(+13»)t477
Moderate
±45(+64)
(+14)382
±62
485 ±34(+63)
512 ±26(+55)Q298
±0 (+19)a
Severe
326 ±56(+16)
328 ±50(-12)
300 ±74( +8)
1Nine rats per dietary group.
* 11 or 12 rats per dietary group.
' Mild diabetic rats included two to four rats per dieatry
group. Moderate diabetic rats included two to five rats per dietary group. Severe diabetic rats included four to seven rats per die
tary group.
*Mean body weight (Mean±so) at the end of experiment with mean weight changes during experimental period in
parenthesis. Mean weight changes in the same vertical column with different superscript letters differ significantly (I1 < 0.05).
cantly higher than values for control rats.
Glucose tolerance tests were also per
formed on moderately and severely diabetic
rats (four rats fed each diet). Plasma glu
cose values were 780 ±115, 785 ±257 and
816 ±135 mg/100 ml at 30 minutes and
640 ±96, 741 ±102, 588 ±94 mg/100 ml
at 90 minutes for the low carbohydrate, the
high sucrose and the starch-bran diets, re
spectively; these differences were not sig
nificantly different. The plasma glucose
values obtained after a glucose load did not
differ significantly between the three di
etary groups for either control or mildly
diabetic rats. Thus, glucose tolerance was
neither exacerbated nor improved in these
control or diabetic rats fed either high car
bohydrate diet when compared with values
for the low carbohydrate diet.
Body weight and weight changes. At the
time of streptozotocin injection, mean body
Downloaded from jn.nutrition.org by guest on May 20, 2013
etary group. After 30 minutes, control rats
had plasma glucose values of 420 ±76
mg/100 ml, 432 ±97, 350 ±107 and dia
betic rats had values of 537 ±221, 535 ±
87 and 534 ±70 for the low carbohydrate,
the high sucrose and the starch-bran diets,
respectively. After 90 minutes, control rats
had plasma glucose values of 238 ±40
mg/100 ml, 215 ±30, and 216 ±24 and
diabetic rats had values of 462 ±197, 399
±98 and 427 ±231 for the low carbo
hydrate, the high sucrose and the starchbran diet, respectively. These mean plasma
glucose values for diabetic rats were sig
nificantly higher than the values for con
trol rats fed the corresponding diet (P <
0.05). Thus these streptozotocin-injected
rats with plasma glucose values <300 mg/
100 ml were considered to be mildly dia
betic because plasma glucose values before
and after glucose injection were signifi
TABLE 4
Liver glycogen in control and diabetic rats
Diabetic
Group 2
Diet
Control
Group 1
Mud
Moderate
Severe
7.6**°(4)53.6±15.1**'(7)22.4
carbohydrateHigh
Low
sucroseStarch-branmg/g56.1±20.3<"(9)82.7±16.96(9)76.0±
±10.8**»(6)
9.9**6(2)mg/g31.4±
9.7»(9)mg/g26.2±11.4**°(12)39.5±12.2**»(12)26.4±10.7**°(12)mg/g37.6Ãœ8.3«(3)86.0±18.86(4)69.9Â
7.3"(2)mg/g23.9±13.7**°(5)60.5±
1MeaniSD with the number of rats in parenthesis.
Means in the same veritcal column with different
superscript letters differ significantly (P < 0.05).
** Significantly different from control rats (P < 0.01).
589
LIPID METABOLISM AND HIGH CARBOHYDRATE DIETS
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weights were similar in control and diabetic
rats. As would be expected, body weights
of control rats were greater than those of
moderately or severely diabetic rats at the
time of killing (table 3).
Control rats had a similar weight gain
with each of the three experimental diets.
Diabetic rats in group 1 fed the high su
crose or starch-bran diets gained signifi
cantly less weight than rats fed the low
carbohydrate diet. The weight gains for
diabetic rats fed the high sucrose and
starch-bran group were similar.
Liver glycogen. The liver glycogen con
tent for control rats fed both high carbo
hydrate diets (high sucrose and starchbran) was significantly higher compared
to the low carbohydrate group (table 4).
These observations are in agreement with
previous studies (6, 7, 34). A significant
increase in liver glycogen was also noticed
in mildly diabetic rats fed high carbohy
drate diets; those rats fed the high sucrose
diet had a similar liver glycogen content
compared to the rats fed the starch-bran
diet.
As anticipated, the liver glycogen con
tent of moderately and serverely diabetic
rats was significantly lower than the value
for control rats fed the corresponding diet.
However, the glycogen content of mildly
diabetic rats was similar to that of control
rats. Studies from other groups (35) have
indicated that early diabetes is accom
panied by a higher concentration of liver
glycogen.
Severely diabetic rats fed the high su
crose diet had a significantly higher liver
glycogen concentration compared to rats
fed the low carbohydrate or starch-bran
diet.
Liver lipid and plasma triglycéride.The
total liver lipid concentrations of control
and diabetic rats fed low carbohydrate
diets were significantly higher than values
for rats fed high sucrose and starch-bran
diets (table 5). This may be related to the
dietary fat since the low carbohydrate diet
contained twice as much fat as the high
carbohydrate diets. No significant differ
ences were observed in total liver lipid
concentration between those rats fed high
sucrose or starch-bran diets.
Liver triglycéridevalues in both control
and diabetic rats were also significantly
590
WEN-JU
LIN AND JAMES W. ANDERSON
TABLE 6
Liver weight, protein content and enzyme activities in control and severely diabetic rats
Liver enzyme
DietLiver
liverLow
nase%
weightLiver
dehydrckinaseG-6-P
enzymentnoles/min/g
genaseMalic
proteinGlucoki
of body weight mg/g
liver65.37±20.88«
9)2.38±0.39°
(n =
carbohydrate
8.73
7.75±3.91» 8.18±4.88*
4.02±1.07' 143.69i24.246
High sucrose
3.58±0.40
91.10± 8.08
4.91
±3.26°0.69±0.35°
±1.77»Severely
110.14±28.75«= 3.30±1.93°1.31
Starch-bran3.46±0.24'3.41 ±0.40Control91.50±
90.18±
5.75rats 4.57
(nLow
diabetic rats*
16)16.97
± 4.62«
carbohydrate
± 5.42
±0.24
5.58±0.446* 98.08±11.22
39.91 ±17.83»1.48±0.33 1.44±0.58k
High sucrose
0.24±0.16
4.11±0.28°*96.58
0.79±0.40°
18.42±
7.97°4.65±1.72°
Starch-bran4.66±0.48°*
1.71±0.282.48±1.31«
97.74± 7.800.18±0.17
0.26±0.29Pyruvate
higher in rats fed the low carbohydrate
diet than values from starch-bran fed rats.
Furthermore, in each of these groups, liver
triglycéridewas significantly higher in the
high sucrose group than in the starch-bran
group. This could not be related to fat in
take since the fat content of these two
high carbohydrate diets was identical.
Plasma triglycéride values followed a
similar pattern to that observed for liver
triglycéride concentrations; values were
significantly higher in both groups ( control
and diabetics) fed the low carbohydrate
diet than those fed the starch-bran diet.
Furthermore, the plasma triglycéridevalue
was higher in the group fed the high su
crose diet compared to the starch-bran
group. The plasma triglycéride value in
these nonfasted control rats is higher than
others have reported for fasted rats (16,
36, 37). The plasma triglycéridevalue for
12-hour fasted rats (47 ±8 mg/100 ml,
n = 12) in our laboratory is similar to the
value reported by others (16, 36).
Diabetic rats had similar total liver lipid
and liver triglycéridewhen compared with
values for control rats fed the correspond
ing diet. However, plasma triglycéride
values for diabetic rats in group 1 fed the
high sucrose or low carbohydrate diets
were significantly higher than the control
rats fed the same diet, whereas those dia
betic rats fed the starch-bran diet had a
significantly lower value than the control
rats. The plasma triglycéridevalue for the
diabetic rats in group 2 followed the same
pattern observed in group 1 but did not
differ significantly from the control value.
Liver enzyme activities. In control rats,
the high sucrose diet was accompanied by
a significant increase in the activities of all
four liver enzymes (table 6). When the
starch bran diet was fed, only glucokinase
and pyruvate kinase activities were signifi
cantly higher than the values for the low
carbohydrate group. Consequently, G-6-P
dehydrogenase and malic enzyme activities
were significantly lower when the starchbran diet was fed than when the high su
crose diet was fed.
Diabetic rats fed the high sucrose diet
had significantly higher pyruvate kinase
and malic enzyme activities than the rats
fed low carbohydrate or starch-bran diet;
the activities of glucokinase and G-6-P de
hydrogenase were similar among those rats
fed the three experimental diets. As noted
previously (38, 39), activities for these four
hepatic enzymes were significantly lower
in severely diabetic rats fed each diet than
in control rats fed the same diet (P < 0.01).
Jejunal enzyme activities. Hexokinase ac
tivities in the homogenate for control rats
fed both high carbohydrate diets were sig
nificantly higher than values for rats fed
low carbohydrate diets (P<0.05),
but
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1MeanisD.
Means within a column with different superscript letters differ significantly (P < 0.05).
1Values of group 1 and group 2 severely diabetic rats were statistically similar and have been pooled.
* Sig
nificantly different from control. (P < 0.05).
LIPID METABOLISM AND HIGH CARBOHYDRATE DIETS
of diabetic rats, 52 ±13%, was significantly
higher than in control rats 32 ±8% (P <
0.05). These observations are consistent
with our previous studies (40, 41) demon
strating that diabetes is accompanied by a
significant reduction in mitochondria-bound
hexokinase activity and by an increase in
the percentage of soluble hexokinase activ
ity in jejunal mucosa.
DISCUSSION
The present study indicates that these
high carbohydrate diets (high sucrose and
starch-bran) did not significantly alter the
glucose tolerance of control rats. This con
trasts with previous studies which have
shown either improvement (6) or deteriora
tion of the glucose tolerance (8, 42) when
normal rats were fed high carbohydrate
diets. These differences may be due to the
genetic or strain differences between the
rats studied since some strains of rats have
an inherited tendency toward glucose in
tolerance (43, 44). Likewise, we were un
able to demonstrate that high carbohydrate
diets altered the glucose tolerance of dia
betic rats.
The glucose tolerance tests were similar
when control rats were fed the high sucrose
diet or the starch-bran diet. This finding is
in contrast with the results of Cohen and
Teitelbaum (8, 45) who reported that glu
cose tolerance was impaired in sucrose-fed
rats compared with the starch-fed rats.
TABLE 7
Jejunal mucosal enzyme activities in control and diabetic rats
Total1 hexo
kinase
Hexokinase2
G-6-P dehydrogenäse2
Pyruvate kinase2
Malic
enzyme2
limóles/min/'g jejunal mucosa
Low carbohydrate
High sucrose
Starch-branLow
Control rats (n = 9)
±1.03'*
8.72±1.126
233.98±58.83'
1.24±0.23
9.21±1.72"7.11±1.99°*
110.14±21.69°(n
±0.18Diabetic
1.35
6.00±1.75
2.70±0.69
3.15±0.753.39±0.84°
4.87±1.866.35±2.46
rats'1.31±0.66°16)160.08±39.86°
carbohydrate
High sucrose
Starch-bran5.51
10.77±1.87l*
4.69±1.65*
1.59±0.50° 203.96±56.91"
7.73±2.39
9.64±2.064*1.34±0.21
4. 13±1.50*
2.08±0.48k127.79±34.05°
119.22±33.34<5.54±1.86
6.90±2.802.66±0.67
1Total hexokinase were measured in jejunal homogenates.
2These four enzymes were measured in
105,000 X g supernatant fractions.
' Mean±8D means within a column with different superscript letters
differ significantly (P < 0.05).
•
Values of group 1 and group 2 diabetic rats were statistically similar and
have been pooled.
* Significantly different from control rats (P < 0.05).
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hexokinase activities in the supernatant
were similar for the high and low carbo
hydrate groups (table 7). These data indi
cate that hexokinase activity in the particulate fraction was increased in control
rats fed high carbohydrate diets. Our pre
vious study (12) suggested that a high
carbohydrate
diet (75% glucose) pro
duced proportionally greater increases in
particle-bound hexokinase activity than in
soluble hexokinase. Pyruvate kinase activity
for control rats fed the high sucrose diet
was significantly higher than the values for
rats fed the low carbohydrate and starchbran diets (P < 0.05). Jejunal G-6-P dehydrogenase and malic enzyme activities
were similar for control rats in the three
dietary groups.
In diabetic rats, hexokinase activity in
homogenate from both high carbohydrate
groups was significantly higher than the
values for the low carbohydrate group
(P<0.05).
Hexokinase activity of the
supernatant fraction in the starch-bran
group was also significantly higher than
values for the low carbohydrate group
(P < 0.05); the activities for the high su
crose and low carbohydrate diet were
similar. Hexokinase activity in the super
natant fraction was higher in diabetic rats
fed starch-bran than in control rats fed the
same diet; homogenate activity was not
increased. Consequently, the percentage of
hexokinase activity in supernatant fraction
591
592
WEN-JU LIN AND JAMES W. ANDERSON
acid synthesis, emphasize the acquired
capacity for enhanced lipogenesis when
rats are fed sucrose (17). Bruckdorfer et
al. (52) pointed out that endogenous
hepatic lipogenesis or fatty acid synthetase
activity may be the major determinant of
triglycérideconcentrations during sucrose
feeding. These metabolic differences be
tween sucrose and starch may be related
to either the fructose moiety in sucrose
(13, 16, 52) or to the dissacharide configu
ration of sucrose (51).
In this study, the higher fiber content of
starch-bran diet ( table 1 ) may be responsi
ble for the lower liver and plasma triglyc
éridevalues in both control and diabetic
rats than values observed when these rats
were fed the high sucrose diet. Dietary
fiber has been demonstrated to exert a
hypocholesterolemic effect in rats (53, 54),
but the influence of dietary fiber on plasma
triglycéride values in rats has not been
carefully evaluated. Our data suggest that
this high carbohydrate
diet containing
starch and wheat bran may have beneficial
effect in lowering the plasma triglycéride
values of diabetic rats.
The effects of diet on carbohydrate and
lipid metabolism in rats were similar in
some instances but differed in other in
stances to that of men. High carbohydrate
diets are associated with improved glucose
tolerance in normal subjects (1, 2), in
mildly diabetic patients (3, 55) and in
moderately to severely diabetic patients
(3-5). Despite the higher hepatic glyco
lytic enzymes for control rats fed the high
carbohydrate diets, we did not see an im
provement in glucose tolerance in these
rats. The lack of improvement in glucose
metabolism of streptozotocin treated rats
with moderate to severe diabetes fed high
carbohydrate diets is consistent with the
observations that glucose metabolism in
untreated moderately to severely diabetic
patients fed high carbohydrate diets is not
improved (3, 20, 21). Since we were un
able to produce mildly diabetic rats, strep
tozotocin treated rats may not be a good
model for studying the influence of high
carbohydrate diets.
Elevations in plasma triglycérideconcen
trations can be induced in men by the feed
ing of diets high in carbohydrate (13, 56-
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These differences could be related to the
observations that different strains have
different responses to sucrose (46). In
diabetic rats, glucose tolerance also was not
altered when responses of rats fed the high
sucrose diet were compared with responses
of rats fed the starch-bran diet.
Triglycéride values in liver and plasma
of control rats fed the high carbohydrate
diet containing sucrose were similar to
values for rats fed the low carbohydrate
diet despite the fact that they had signifi
cantly higher glycolytic and lipogenic en
zyme activities. These data differ from pre
vious observations that high carbohydrate
diets increase the liver (36, 47, 48) and
plasma triglycéridevalues (7, 34, 45) in
normal rats. The incorporation of [6-14C]glucose, [6-14C]fructose or 14C acetate into
hepatic fatty acids are higher in rats fed
high carbohydrate diets than in animals
fed a stock diet (16, 47). Waddell and
Fallón (48) demonstrated that high carbo
hydrate diets increased the capacity for
triglycéride formation from a-glycerol-3phosphate in rat liver homogenates and
also increased the incorporation of [1,314C] glycerol into hepatic triglycéride in
the intact animal. The activities of the en
zymes supporting lipogenesis, G-6-P dehydrogenase, NADP-malate dehydrogenase
and acetyl CoA carboxylase, are also higher
in animals fed high carbohydrate diets
(17, 47). Even in diabetic rats, however,
our studies demonstrate that the values of
liver and plasma triglycéridefor rats fed
the high sucrose diet are not different from
the values for rats fed the low carbohydrate
diet.
Many investigators have reported that
high sucrose diets result in higher liver
and plasma triglycéridevalues (17-19, 49,
50) and are associated with higher G-6-P
dehydrogenase and malic enzyme activities
( 17, 50, 51 ) than the values observed with
starch diets. These observations are con
firmed by the present study demonstrating
that sucrose feeding was accompanied by
elevated liver and plasma triglycéride
values. The remarkable rises in the activ
ities of liver enzymes for NADPH produc
tion and especially the more than five
fold rise in the activity of acetyl-CoA car
boxylase, which is directly involved in fatty
LIPID METABOLISM AND HIGH CARBOHYDRATE DIETS
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
ACKNOWLEDGMENT
This work was performed in the Meta
bolic Research Laboratory (MRIS #0403)
and was supported, in part, by grants from
the Upjohn Company and the Berk Foun
dation.
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