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Journal Vol. 46, ofNo. Clinical 2, 1967 Investigation
Effect of Diet upon Intestinal Disaccharidases and
Disaccharide Absorption *
J. J. DEREN, S. A. BROITMAN, AND N. ZAMCHECK t
(From the Gastroenterology Laboratory, Mallory Institute of Pathology; the Second and Fourth [Harvard] Medical Services, Boston City Hospital; the Department of Medicine, Harvard Medical School; and the Departments of Microbiology and Pathology, Boston University School of Medicine, Boston, Mass.)
Summary. The administration of a carbohydrate-containing diet for 24
hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of (^) mal- tase was similarly increased, but lactase activity was unaffected. The (^) su- crose-containing diet led to a greater increase in sucrase than maltase ac- tivity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase ac-
tivity of mixed homogenates from casein-fed and sucrose-fed rats or fasted
and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the ab- sence of steroidal (^) control on sucrase and maltase activity in the adult (^) animal.
Studies using intestinal ring preparations indicated that sucrose hydrolysis
by the^ intact cells proceeded more rapidly when animals were^ fed^ sucrose. Additional corroboration of the physiologic significance of the increased^ en-
zyme levels in homogenates was afforded by intestinal perfusion studies.
Sucrose hydrolysis increased twofold and fructose absorption fourfold^ in
animals fed sucrose when compared to either fasted or casein-fed rats.
Introduction
The demonstration of isolated deficiencies of
the intestinal disaccharidases as well as the non-
specific depression of these enzymes in^ diverse
small (^) bowel diseases has renewed interest in (^) disac-
charide absorption (1-5). To^ date, little is known
- (^) Submitted for (^) publication June 6, 1966; accepted October 20, 1966. This investigation was supported by research grants T1 AM 5320, National Institute of Arthritis and Meta- bolic Diseases; CA 02090 and CA 04486, National Can- cer Institute; and GMO 9628, National Institute of Gen-
about the factors that regulate the tissue levels of these enzymes and their physiologic significance.
Marked variability of disaccharidase levels char-
acterizes the peroral biopsy specimen in normal humans and is due in part to variable numbers of
eral Medical Sciences, National (^) Institutes of Health, Bethesda, Md. A preliminary report appeared in Fed. Proc. 1965, 24, 403. t Present address: Dept. of Medicine, State University of New York (Downstate) and Dept. of Medicine, Maimonides Hospital, Brooklyn, N. Y. t Address requests for reprints to Dr. N. Zamcheck, Boston City Hospital, Boston, Mass. 02118. 186
DISACCHARIDASES AND DISACCHARIDE ABSORPTION
epithelial cells and inflammation within the lamina propria. Furthermore, enzyme activity may be in- fluenced by previous dietary experience. In the rat at least, intestinal sucrase (6) and alkaline phosphatase (7, 8) can be modified by diet. Al- though evidence on this point is not available in humans, there is little doubt that enzymatic adap- tation occurs in mammalian tissue and that this may be induced by appropriate substrates. How- ever, the relationship of adaptation to physiologic function is not well defined. Thus, depressed lev- els of disaccharidases can be implicated as func- tionally significant in disaccharide malabsorption only if the enzyme level is rate-limiting and varia- tions in^ disaccharidase levels are reflected^ by changes in disaccharide absorption. We initiated the present studies 1) to determine the influence of diet and adrenocorticoid hormones upon intestinal disaccharidase levels, 2) to define the mechanism, and 3) to study the physiological significance of these changes measured in vitro and in Z'IVO.
Methods Male albino rats 1 (175 to 350 g) were kept at constant temperature (70 10 F) for at least 1 week before ini- tiation of the experiment, during which time they were fed Purina laboratory chow ad libitum. The rats were fasted but allowed water ad libitum for 3 days, and then they were placed for 24 hours on one of the synthetic diets (Table I). Adrenalectomized rats (maintained with lo% sodium chloride in their drinking water) were fasted but allowed free access to 1%o sodium chloride solution for 24 (^) hours; then they were placed on one of the synthetic diets for 24 hours. Homogenate (^) assays. Rats were decapitated and^ the small bowel rinsed in situ with ice-cold (^) 0.9%o saline. The entire small bowel or the third 10-cm segment distal to the pylorus was removed and homogenized in seven times its volume of cold saline in a glass homogenizer. We assayed samples as described below at various dilutions and different time intervals to ensure linearity of the assays. Although maltose and sucrose are hydrolyzed by several apparently different enzymes with overlapping substrate affinities, for convenience the enzymes that hy- drolyze each substrate are referred to collectively as sucrase or maltase. Sucrose hydrolysis by intestinal rings. The entire small bowel was rinsed in, (^) situ with (^) ice-cold saline, re- moved, everted with a metal probe, and cut into rings weighing 20 to 30 mg each according to the general method of Agar, Hird, and Sidhu (9). After randomi- zation, ten to fifteen rings were placed in an Erlenmeyer (^1) Charles River Laboratories, Wilmington, Mass.
TABLE I Synthetic diets
Substance content^ Dietary g/100 g diet Sucrose, maltose, glucose, fructose, or vitamin-free casein 68 Casein (vitamin-free) 17 Beef fat 8 Salt mixture* 4 Cellulose flour 2 Vitamin powdert 1
- (^) Salt mixture contained Ca(C3H502)2-5 H20, 35%; CaCO3, (^) 5.06%; Ca(H2PO4) -H20, (^) 14.6%; K2HPO4, 6.46%; NaH2PO4-H2O, 18.76%; NaCl, 9.34%; MgSO4, 7.18%;
ZnSO4, 0.035%; CuSO4, 0.039%70; KI, 0.00039%; Fe
citrate, 3.2%; and MnSO4 H2O, 0.33%. t Vitamin powder contained thiamine, 0.05%; riboflavin, 0.025%; pyridoxine, 0.02%; calcium pantothenate, 0.1%; and nicotinic acid, 0.1%.
flask containing 20 ml of 28 mM d(+)-sucrose 2 and 1% polyethylene glycol 3 (4,000) (PEG) in a phosphate- saline buffer (pH 7.4) and incubated at 370 C in a shak- ing water bath. Samples of the incubation medium were removed at 30, 45, and 60 minutes and analyzed for PEG, fructose, glucose, and sucrose. An estimate of su- crase activity was obtained by homogenizing a sample of the rings in cold saline and assaying in a phosphate- saline buffer that contained 28 mM sucrose (pH 7.4). Perfusion studies. Rats were fasted and refed as de- scribed above. A general method described by Schanker, Tocco, Brodie, and Hogben was used in the perfusion studies (10). The rat was anesthetized with Pentothal (5 mg per 100 g body weight) and placed in an incuba- tor maintained at 370 C. A ligature was placed around the pylorus, a small incision was made in the first por- tion of the duodenum, and a cannula was inserted. After the ileocecal area had been ligated, a polyethylene cathe- ter was inserted into the distal ileum. A^ solution con- taining 18 to 20 mM sucrose in 140 mM^ NaCl with^ 1% polyethylene glycol maintained at 37° C was perfused by a constant perfusion pump 4 for 30 minutes^ at^ 1.5^ ml^ per minute, and the effluent was discarded. Six consecutive 10-minute collection periods were obtained; the^ effluents were assayed for sucrose, glucose, fructose, and^ PEG^ as described below. The per cent water absorption was^ de- termined from the change in^ PEG^ concentration^ (11). Analytical methods. Sucrase, maltase, and^ lactase^ ac- tivities were determined as described^ by Dahlqvist (12) with minor modifications.^ Sucrase and maltase activities were measured in a 25 mM sodium maleate buffer (^) (pH 6.2) with^ the^ substrate^ at^ a^28 mM^ concentration^ except where otherwise specified; lactase activity was measured in a phosphate-citrate buffer (pH 4.8) with lactose^ pres- ent at 14 mM concentration. Alkaline^ phosphatase was measured as described by Moog (13) using 100 mM^ so- (^2) Mallinckrodt Chemical Works, St. Louis, Mo. (^3) Union Carbide (^) Corp., New (^) York, N. Y. (^4) Harvard Apparatus Co., Dover, Mass.
187
DISACCHARIDASES AND DISACCHARIDE ABSORPTION
TABLE III Total intestinal sucrase activity of rats fed various dietary regimens*
No. of Meanbody Total intestinal Diet animals wt Total gut protein Specific activity sucrase activity g g 5moles hydrolywed/gprotein/min pmoles hydrolyzed/min Fasted 15 165 0.564 4- 0.031 20.0 4 1.79 10.8 i 1. Casein 16 164 0.723 i 0.039 25.8t ± 1.30 18.7$ i 1. Sucrose 16 165 0.688 + 0.031 46.1$ i 2.74 (^) 31.5T i 2.
Fructose 6 135 0.766 i 0.116 45.51 i 3.88 33.7$ ± 4.
Glucose 7 136 0.760 i 0.071 (^) 43.4t ± 2.06 (^) 27.3t 4t 3. Maltose 16 165 0.670 :1: 0.040 (^) 36.4$ i 2.89 (^) 23.6t ± 1.
- (^) Results are expressed as means ±^ standard errors. t $ p < 0.05 > 0.01 when compared to fasted animals. p <^ 0.01^ when^ compared to^ fasted^ animals.
the specific activity of sucrase. The casein-con- taining diet yielded a minimal increase in sucrase specific activity owing to the increased gut pro- tein in this group. Total intestinal sucrase activity was, however, significantly increased in the casein- fed animals as compared to fasted controls.
Changes in sucrase activity observed with the
different dietary regimens may represent changes
in the quantity of enzyme present or alterations in
the kinetic characteristics of a similar quantity of enzyme. Accordingly, the following studies were performed. Jejunal homogenates from sucrose- and casein-fed rats were prepared, and sucrase ac- tivity was determined. Portions of each fraction were mixed together; the sucrase activity of the mixed homogenates was measured (Table IV). The sucrase activity of the mixed homogenate was not significantly different from that predicted on
the basis of an additive effect. Similar results
wvere obtained from mixed homogenates from su-
crose-fed and fasted animals, indicating that the
differences observed were not attributable to vari-
ations in easily dissociable inhibitors or activators.
TABLE IV Mean sucrase activity of mixed homogenates from fasted, sucrose-fed, and casein-fed rats* Mixed homogenates Theoret- (^) enceMean differ- between Obtained ical pairs ±SE Sucrose Casein 26.7 (6) 15.7 21.9 21.5 0.33±40. Sucrose Fasted 32.6 (5) 11.3 23.8 22.6 1.2 ±0.
- (^) The results are (^) expressed as micromoles sucrose hydrolyzed per gram gut number of protein per minute and are given as the (^) mean value. The experiments is^ given in^ parentheses.
Intestinal sucrase activity of fasted or sucrose- or casein-fed rats was (^) assayed at different sub- strate concentrations. At each substrate concen- tration (^) the homogenates from sucrose-fed (^) rats exhibited greater sucrase activity than homoge- nates from casein-fed and fasted animals (Figure 2). However, the curves approached saturation at similar^ substrate concentrations.^ When these data were (^) plotted by the method of Lineweaver and Burk (^) (Figure 3), the Km of the enzyme or en-
zymes hydrolyzing sucrose^ was^ similar^ in^ the
fasted and casein- or sucrose-fed rats. The (^) Vmax,
\60-
20 ~AS~M
I * I (^). * I INITIAL SUCROSE CONG.. mM FIG. 2. SUCRASE ACTIVITY OF HOMOGENATES OF ENTIRE SMALL INTESTINE OF FASTED, SUCROSE-FED, AND CASEIN- FED RATS AT VARYING SUBSTRATE CONCENTRATIONS. Sam- ples were assayed in a maleate buffer (pH 6.2) at varying substrate concentrations. Incubation was carried out at 370 in a shaking water bath, and samples were removed at different time intervals to ensure the linearity of the assay. There were three rats in each group; the values listed represent the mean values obtained on duplicate determinations.
189
J. J. DEREN, S. A. BROITMAN, AND N. ZAMCHECK
-.05 0 .05 0.1 Q. [SUBSTRATE] FIG. 3. LINEWEAVER AND BURK PLOT OF DATA FROM FIGURE 2. Km =^ Michaelis constant; Vmax =^ maximal velocity.
however, was twice as great in sucrose-fed as^ com- pared to casein-fed or fasted rats. As corticosteroids have been shown to^ induce precociously sucrase activity in developing rat in- testine (18) and to induce many other mammalian enzymes (19), the effects of adrenalectomy and subsequent steroid replacement were studied (Ta- ble V). Levels of sucrase and maltase in adrenal- ectomized rats that were fed casein while being
maintained on a 1.0%c salt intake in their drinking
water were in the range found in nonadrenalec- tomized rats fed the casein diet. Cortisone acetate administration (3 mg per 100 g body weight in three divided doses) did not significantly increase their activities. Sucrose feeding, however, elicited a rise in sucrase and maltase activities of an order of magnitude observed in the nonadrenalectomized rats. To determine whether the rise in intestinal en- zymes was limited to sucrase and maltase, we mea- sured intestinal alkaline phosphatase activity. Both the casein and sucrose diets elicited a significant rise in the intestinal alkaline phosphatase. Both
diets contained 17% fat, which presumably was
responsible for a rise in intestinal alkaline phos- phatase activity (7). This^ was^ circumvented^ by fasting two groups of^ rats^ for^3 days;^ one^ group had access to a 20%o solution of sucrose for 24 hours, whereas the other had access only to water. Rats drinking the sucrose solution had a signifi- cant rise in intestinal sucrase activity, but alkaline phosphatase activity rose only slightly and did not
achieve a 5% level of significance (Table VI).
To determine whether the differences in sucrase levels in homogenates of fasted^ as^ compared^ to
sucrose-fed rats were of physiological significance,
we measured the rate of sucrose hydrolysis by in-
tact cell preparations using both in^ 7itro^ and^ in
vivo techniques. In^ ring preparations,^ the^ rate^ of
sucrose hydrolysis proceeded more^ rapidly^ with
rings prepared from^ sucrose-fed^ rats^ as^ compared to those of fasted^ animals^ (Figure^ 4). These findings were further corroborated with
intestinal perfusion studies in vivo. Rats fed the
different dietary regimens were^ perfused^ at^ a^ con-
stant rate, and the^ rates of sucrose,^ glucose, and
fructose appearing in^ the^ effluent^ were^ measured
(Table VII). In^ the^ fasted^ animals,^ when^ sucrose was perfused at 28.2 (^) pLmoles per^ minute,^ 8. ,umoles per^ minute^ was^ hydrolyzed,^ and^ 5.8^ ,fmoles
of fructose per minute appeared in^ the^ effluent for
a net absorption of 2.2^ pumoles^ of^ fructose^ per^ min-
ute. At a similar perfusion rate, rats^ fed^ sucrose
for 1 day hydrolyzed 14.4^ Ftmoles of^ sucrose^ per minute; 5.5 Mmoles per minute of^ fructose^ ap-
peared in the effluent for^ a^ calculated^ net^ absorp-
tion of 8.9 (^) /.Lmoles per minute.^ Perfusion^ of^ rats fed sucrose for 7 days yielded similar^ results.
Casein-fed rats hydrolyzed sucrose^ at^ a^ rate^ be-
tween that of the fasted and sucrose-fed animals
(10.8 (^) jumoles per minute), whereas fructose^ was absorbed at a rate of (^) 2.6,umoles per minute.^ Wa-
ter absorption was similar in^ all^ groups.
Discussion
The present^ report^ confirms the^ observation^ that
diet influences intestinal^ sucrase, maltase,^ and^ al-
TABLE V Comparative effects offeeding casein,^ casein +^ cortisone,^ and sucrose on jejunal sucrase and maltase activities of adrenalectomized rats* Diet Sucrase^ activity Maltase^ activity
hydrolyzed/g/min^ 5moles^ sucrose^ hydrolyzed/g/minpmoles^ maltose Casein 27.4^ ±2.1^ (10) 80.7^ ±4.1^ (10) Casein + cortisone 36.4t± 1.9^ (6) 84.9t-3.2^ (6) Sucrose 67.1+±2.2 (10) 1301 ±8.5 (10)
- (^) The third 10-cm segment of small bowel distal to the pylorus was homogenized and^ assayed for^ sucrase^ and maltase. Results are expressed as^ mean^ values^ ±^ standard errors. The number of^ animals^ is^ given in^ parentheses. t p >^ 0.05^ as^ compared to^ casein-fed^ rats. t p < 0.01 as (^) compared to casein-fed rats.
J. J. DEREN, S. A. BROITMAN, AND N. ZAMCHECK
TABLE VII Small bowel sucrose perfusions of fasted and sucrose- and casein-fed rats*
Sucrose in-^ Water Effluent Sucrose Fructose Group fusion rate absorption Sucrose Fructose hydrolysis absorption jumoles/min % tmoles/min^ jumoles/min^ pmoles/min 3-day fast (17) 28.2 i 0.3 5.4 i 0.8 20.2 i 0.5 5.8 i 0.4 8.0 i 0.4 2.2 ± 0. 3-day fast + 1-day casein diet (8) 28.8 i 0.7 6.8 i 2.1 18.0 i 1.1 8.2 ±^ 1.0 10.8t i 0.8 2.6 ± 0. 3-day fast + 1-day sucrose diet (8) 28.2 i 0.3 7.0 ±^ 1.6 13.8 i 0.7 5.5 i 0.4 14.4§ ±^ 0.7 (^) 8.9§ i 0. 3-day fast + 7-day sucrose diet (4) 28.3 i (^) 0. 9 7.2 i 2.4 11.4 i 3.0 6.0 ± 0.8 16.9§ i 2.2 10.95 i 2.
- (^) Results are expressed as mean values i standard errors. The number of animals per group is in parentheses. t p < 0.01 when^ compared to^ fasted^ rats. t p § <^ 0.05^ when^ compared to^ fasted^ rats. p < 0.01 when compared to fasted and casein-fed rats.
with the greater increase in total intestinal sucrase activity elicited by sucrose feeding.
Glucose derived from sucrose hydrolysis in
fasted and casein- and sucrose-fed rats was almost completely absorbed as minimal quantities of glu- cose appeared in the ileal effluent. Fructose, how- ever, was not completely absorbed. In fasted rats approximately 25%o of the fructose liberated by hydrolysis was absorbed. In casein-fed animals,
the quantity of fructose formed subsequent to su-
crose hydrolysis increased slightly and was fol- lowed by a proportional increase in fructose ab- sorption. In the sucrose-fed rats, twice as much sucrose was hydrolyzed as compared to fasted ani-
mals. However, four times as much fructose was
absorbed. This can be explained in part by the higher luminal concentration of fructose achieved in the sucrose-fed rats and the greater fructose absorption in^ sucrose-fed as compared to fasted animals (21). Thus, changes in intestinal su- crase (^) activity paralleled an increased ability of the intestine to both hydrolyze this substrate and ab- sorb constituent monosaccharides. Alterations in cell permeability subsequent to carbohydrate feeding cannot be discounted in the present study. Increased cell permeability may al- low more rapid access of the disaccharide to the active enzyme site within the cellular compart- ments-a postulated prerequisite to hydrolysis
into constituent monosaccharides (22, 23). With
intact cell preparations, Dahlqvist and Thomson
(24) have shown that at low substrate concentra- tions the limiting step is the rate at which^ the
substrate molecules^ traverse^ the^ cell^ boundary.
As the substrate concentration is increased, the
activities of^ homogenates and^ intact^ cells^ ap- proach each other with a similar Vmax. At 28
mmoles per L, the concentration employed in this
study, the^ rate^ of^ cellular^ entry may be rate-limit-
ing. However, it is unlikely that a twofold in-
crease in sucrose hydrolysis could be explained
entirely on the basis of altered cell permeability.
On the other hand, the entry of disaccharides into
a cellular compartment before^ hydrolysis has^ not
been clearly delineated. Indeed, it has been^ sug-
gested that the disaccharidases^ may be situated at
the luminal surface of^ the^ plasma membrane^ on^ the
microvillus (25). Hydrolysis may thus^ be^ totally
or at^ least partially intraluminal.^ In this^ case, the
increased rate of sucrose hydrolysis observed^ in
vivo is explained entirely by the^ increase in^ en-
zyme activity observed in^ homogenates.
In mammalian systems, enzymatic adaptation
may occur via several mechanisms, i.e., a^ change
in the affinity of^ the^ apoenzyme for the^ cofactor,
new enzyme synthesis, or^ an^ increased^ quantity of
enzyme subsequent to^ a^ decreased^ degradative rate
(26, 27). The increased^ disaccharidase^ activity
observed in these studies is presumably secondary
to an increase in the quantity of enzyme. The ad-
ditive effects observed when mixed homogenates
from fasted and sucrose-fed rats^ were^ assayed are
192
DISACCHARIDASES AND (^) DISACCHARIDE ABSORPTION
indirect evidence for an increased quantity of en-
zyme. The similar Km of the (^) enzymes hydrolyz- ing sucrose in both fasted and sucrose-fed rats with a twofold greater Vmax in the latter animals is best explained by the presence of twice the quan- tity of enzyme in the sucrose-fed rats. Direct con- firmation of this hypothesis (^) would require assay of the quantity of enzymes by means independent of activity measurements, as has been shown im-
munologically with other enzymes (28, 29).
It has been suggested that the mechanism regu- lating enzyme levels in the adult may be similar to those regulating the accumulation of the en- zyme in the developing organism (29). Although rat intestinal (^) sucrase may be precociously induced by steroids (19) and its appearance delayed in an adrenalectomized rat (30), sucrase and maltase levels in the adult were not affected by adrenalec- tomy or steroid administration. Rat intestinal maltase has been previously observed to be unal- tered after adrenalectomy (31). However, as (^) the half-lives of the intestinal sucrases are unknown, caution must be exercised in the interpretation of the lack of (^) steroidal stimulation. Schimke, Swee- ney, and Berlin (32) have shown that the rise in enzyme activity after steroid or substrate ad- ministration is related to the half-life of the en- zyme. The lack of steroid stimulation may merely indicate a prolonged half-life, so that during the
period of observation after the stimulus has been
applied only a small portion of the (^) enzyme mole- cules have had a chance to turn over. However, as a 24-hour fast leads to a (^) 50% reduction in in- testinal sucrase, it would appear that these en- zymes are (^) turning over at a rapid rate. The histology of the small intestine from fasted and casein- (^) and disaccharide-fed animals did not
significantly differ. However, it is possible that
even during short periods of dietary manipula-
tion, changes in intestinal epithelial cell popula-
tion may occur as the epithelium is turning over at a rapid rate (33, 34). Consequently, mea- surements of the total epithelial cell population would be (^) required to demonstrate that the en-
zyme changes observed represented a change in
the number of enzyme molecules per cell rather
than an increase in cell population.
In the absence of such measurements, enzyme
activity is^ expressed in terms of wet or dry weight
or of nitrogen content. Clinical interpretation of
these results is further limited when they are ob-
tained on fragments of human intestinal mucosa.
In addition to the epithelial cells, many other cel- lular constituents of these biopsy specimens in-
cluding inflammatory infiltrates of the lamina pro-
pria are included in homogenates prepared for en- zyme analysis. Since it is accepted that disacchari-
dase activity resides in the brush border of the
epithelial cells, the enzymatic activity may be (^) arti- factually lowered by the protein contribution of in-
flammatory cells. An additional factor contributing
to the variability noted in the peroral biopsy speci-
mens of normal individuals may relate to the die- tary intake preceding the biopsy. Moreover, pa- tients who experience symptoms after the intake of certain food products are (^) likely to refrain (^) from them, so that any depression of measured physio- logical function may result in part at least from lack of suitable "substrates" induction. (^) It would appear to be important to determine whether die- tary factors similarly influence disaccharidases and disaccharide absorption in human subjects. In- deed, changes in intestinal disaccharidases (^) have been reported in human subjects after periods (^) of prolonged fasting (35). Previous attempts to in- duce lactase activity in deficient adults by feeding milk have not been successful (^) (36). However, lactase may be less responsive to dietary manipula- tion, as evidenced by the failure to acutely induce lactase activity in (^) experimental animals. Under conditions of prolonged ingestion of large quan- tities of lactose, total lactase activity in rats has been reported to increase, secondary to an increase
in total gut weight and length, but without an in-
crease in lactase specific activity (37, 38). Con-
versely, others have reported a statistically sig-
nificant increase in lactase activity after prolonged (6 to 9 weeks) ingestion of lactose (39).
193
DISACCHARIDASES AND DISACCHARIDE ABSORPTION
- Levin, R. J., H. Newey, and D. H. Smyth. The effects of adrenalectomy and fasting on intestinal function in the rat. J. Physiol. (Lond.) 1965, 177, 58.
- Schimke, R. T., E. W. Sweeney, and C. M. Berlin. An analysis of the kinetics of rat liver tryptophan pyrrolase induction: the significance of both en- zyme synthesis and (^) degradation. Biochem. bio- phys. Res. (^) Commun. 1964, 15, 214.
- (^) Thaysen, E. H., and (^) J. H. (^) Thaysen. Morphological changes in^ the^ gastrointestinal tract of the white rat following inanition. Acta path. microbiol. scand. 1949, 26, 370.
- Hooper, C. S., and M. Blair.^ The^ effect^ of starva- tion on epithelium renewal in the rat (^) duodenum. Exp. Cell Res. 1958, 14, 175.
- Knudsen, K. B., H. M. Bellamy, R. R. Lecocq, E. M. Bradley, and J. D. Welsh. The influence of fast-
ing and refeeding on jejunal disaccharidases. Clin. Res. 1966, 14, 300.
- Cuatrecasas, P., D. H. Lockwood, and J. R. Cald- well. Lactase deficiency in the adult: a common occurrence. Lancet 1965, 1, 14.
- Fischer, J. E. Effects of feeding a diet containing lactose upon (^) P-D-galactosidase activity and organ development in the rat digestive tract. Amer. J. Physiol. 1957, 188, 49.
- Huber, J. T., R. J. Rifkin, and J. M. Keith. Effect of level of lactose upon lactase concentrations in the small intestines of young calves. J. Dairy Sci. 1964, 47, 789.
- (^) Giradet, P., R. (^) Richterich, and I. Antener. Adapta- tion de la lactase intestinale a l'administration de lactose chez le rat adulte. Helv. physiol. Pharma- col. Acta 1964, 22, 7.
