Human and Clinical Nutrition
Raw Soybeans Stimulate Human Pancreatic
Proteinase Secretion1
HALVOR HOLM, JANNE E. RESELAND, * LILL I. THORSEN, *
AUDUN FLATMARKr AND LARS E. HANSSEN**
Institute for Nutrition Research, university of Oslo, N-0316 Oslo, Norway,
*MATFORSK-Norwegian Food Research Institute, Osloveien 1, N-1430 Aas, Norway, and
1Surgical Department B and **Medical Department, Rikshopitalet, N-0027 Oslo, Norway
ABSTRACT Intraduodenal instillation of raw soybeans
stimulated pancreatic proteinase secretion in humans.
Raw soybeans almost abolished the activity of
chymotrypsin and severely reduced (50%) the tryptic
activity. Immunoreactive tryptic and chymotryptic ma
terial simultaneously appeared in amounts 2 to 4 times
basal concentrations. This increase, demonstrated with
rocket immunoelectrophoresis, was begun within the
first 10 min of soybean instillation. The enhanced se
cretion also persisted throughout the succeeding saline
instillation, and it is suggested that the presence of
Kunitz trypsin inhibitor contributed to this postprandial
stimulation. An amidase that hydrolyzes low-molecular-
weight substrates (i.e., benzoyl-arginine p-nitroanilide)
was found in raw soybeans. Its low activity was not
assumed to substantially bias standard trypsin assays.
The increased proteinase secretion was, as previously
published, not preceded by an elevated plasma
cholecystokinin concentration. The raw soybeans also
caused a nonparallel secretion of amylase and protein-
ases. Nervous, perhaps cholinergic, regulation mediates
the inhibitor-stimulated proteinase secretion in humans.
This stimulation yields both a general increase of pro-
teinases and also a specific inhibitor-resistant trypsin.
This is consistent with the physiologic need for
proenzyme-activation in the presence of inhibitors and
for restoration of the proteolytic capacity of the duodenal
juice. J. Nutr. 122: 1407-1416, 1992.
INDEXINGKEYWORDS:
•cholecystokinin •feedback regulation
•humans •trypsin •soybean amidase
•soybean proteinase inhibitors
The feedback regulation of pancreatic secretion in
humans has been debated (Adler et al. 1989, Owyang
et al. 1986a). In rats, the animal most frequently used
as a model, a feedback regulation seems well docu
mented on the basis of certain levels of free trypsin in
the duodenum and plasma cholecystokinin (CCK).2
Reduction of tryptic (and chymotryptic) activity by
proteinase inhibitors, or by diversion of pancreatic
juice, causes a prompt increase in plasma CCK that in
turn stimulates pancreatic enzyme secretion (Fushi et
al. 1989, Liddle et al. 1984, Miyasaka and Green
1984). Continued CCK stimulation causes hyper-
thropy and hyperplasia, resulting in nodules and later
in neoplastic changes in the rat pancreas (Liener et al.
1985).
In a recent study (Holm et al. 1988a) raw soybeans,
a soybean protein isolate or bovine serum albumin
were continuously instilled into human duodena on
different days while intermittent samples of blood
and duodenal juice were collected. Only when bovine
serum albumin was instilled was a significant in
crease in plasma CCK found. Parallel to this increase
in CCK, increases in trypsin (EC 3.4.21.4)
chymotrypsin (EC 3.4.21.1) and amylase (EC 3.2.1.1)
activities were also found. The CCK concentrations
during soybean protein isolate and raw soybean instil
lations were almost identical to the basal CCK levels.
A considerably larger increase in proteinase activities
was seen during the soybean protein isolate instilla
tion, whereas the raw soybeans caused a substantial
inhibition of proteolytic activity. Although the
tryptic and the chymotryptic activities varied consid
erably, no significant difference could be seen in the
amylase activity when any of the three test proteins
was instilled. In two similar instillation experiments
with proteinase inhibitors, a general stimulation
'Supported by the Anders Jahres Foundation and the Norwegian
Cancer Society.
Abbreviations used: BAPNA, Mx-DL-arginine p-nitroanilide;
BTEE, Mx-benzoyl-L-tyrosine ethyl ester,- CCK, cholecystokinin;
ODn, optical density at n nm; S-2677, Af-t-butyloxycarbonyl-L-
glutamyl-(ot-O-benzyl)-glycyl-arginine-p-nitroanilide-HCl; SBTI,
Kunitz soybean trypsin inhibitor,- TTBS, tris-tween buffered saline.
0022-3166/92 $3.00 ©1992 American Institute of Nutrition. Received 8 luly 1991. Accepted 25 February 1992.
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