42(2):151-155,2001
CLINICAL SCIENCES
Effect of Oral Glucose Loading on Serum Gastrin Level in Pregnant and
Non-pregnant Women
Fatih Gultekin, Mehmet Gurbilek1, Husamettin Vatansev1, Sulhattin Yasar2, Mehmet Akoz1, Mustafa
Ozturk3
Department of Biochemistry and Clinical Biochemistry, School of Medicine, Suleyman Demirel University, Isparta,
1Department of Biochemistry, School of Medicine, Selcuk University, Konya, 2Discipline of Feeds and Nutrition,
Department of Animal Science, Agricultural Faculty; and 3Department of Public Health, School of Medicine, Suleyman
Demirel University, Isparta, Turkey
Aim. To evaluate the relationship between the changes in gastrin and insulin serum concentrations after oral glucose loading in
pregnant and non-pregnant women.
Methods. Thirty women, 12 pregnant and 18 non-pregnant, with normal fasting glucose values were included in the study. Serum concentrations of gastrin, glucose, insulin, and glucagon were analyzed at 0 (t1), 30 (t2) and 60 (t3) minutes after 75 g oral
glucose loading. Gastrin, insulin, and glucagon levels were determined by means of radioimmunoassay kits.
Results. Serum gastrin concentration in pregnant women increased insignificantly (gastrin median values 57.91, 70.62, and
68.70 for t1, t2, and t3, respectively; Friedman’s test, p=0.264). In non-pregnant women gastrin levels insignificantly increased from t1 to t2, but reduced significantly from t2 to t3 (gastrin median values 62.91, 86.92, and 62.25 for t1, t2 and t3, respectively; Bonferroni adjusted Wilcoxon test, p=0.002). Unlike in pregnant women, the changes in gastrin release in
non-pregnant women were associated with changes in blood glucose concentrations at t2 and t3, which were induced by oral
glucose loading. Glucose median values were 7.48 and 6.43 for t2 and t3, respectively. The insulin release due to the oral glucose loading markedly increased at t2 and t3 (Friedman’s test, p<0.001), whereas glucagon release decreased irrespective of
pregnancy.
Conclusion. Changes in blood glucose concentrations induced by oral glucose loading could influence gastrin release, especially in non-pregnant women. Changes in insulin and glucagon levels induced by oral glucose loading, particularly after 60
minutes, could not be associated with changes in gastrin release.
Key words: administration, oral; blood glucose; glucose; glucagon; gastrin; insulin; pregnancy
Gastrin, the major hormonal factor during the gastric phase of acid secretion, is secreted in response to
antral distention and presence of food and partially digested protein products (peptides and polypeptides) in
the stomach (1). Any free amino acids present also stimulate gastrin secretion, whereas fats have little effect on
gastrin release. Vagal stimulation initiated by smelling,
tasting, chewing, and swallowing of food also stimulates
gastrin release (1). Some studies demonstrated that
hyperglycemia reduces gastrin release previously increased by some stimulators (2). For instance, intravenous administration of amino acids stimulates gastrin release, which is subsequently inhibited by the
hyperglycemia induced by intravenous infusion of glucose (2). It has also been reported that meal-stimulated
gastrin release significantly decreases during
hyperglycemia (3). In healthy subjects, infusion of insulin, with subsequent hypoglycemia, stimulates acid secretion (4,5), whereas infusion of glucose to induce
hyperglycemia inhibits basal pentagastrin, sham feeding,
and meal-stimulated acid output (6-8). Thus, the gastrin
release seems to be directly or indirectly mediated by
hormonal, neural, and metabolic changes secondary to
hyperglycemia.
Hyperglycemia causes an inhibition of gastrin release
and increases insulin secretion (4). However, insulin does
not inhibit gastric acid secretion, but stimulates acid output
only during hypoglycemia (4). In contrast to the studies of
inhibitory effect of hyperglycemia induced by intravenous
glucose administration on gastrin release (2,6-8), no studies have been conducted to determine the effect of orally
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Gultekin et al: Gastrin Release After Glucose Loading
(4). In contrast to the studies of inhibitory effect of
hyperglycemia induced by intravenous glucose administration on gastrin release (2,6-8), no studies
have been conducted to determine the effect of
orally taken glucose on the gastrin release without
inducing hyperglycemia. The aim of this study
was to determine serum gastrin, glucose,
glucagon, and insulin concentrations after oral administration of 75 g glucose, and to evaluate the
changes in and relations between the above parameters. Since pregnancy induces hormonal
changes (9-12), serum concentrations of gastrin,
glucagon, and insulin were monitored in nonpregnant and pregnant women.
Subjects and Methods
Subjects
The clinical trial was carried out in the Mother and
Child Health Center in Konya, Turkey, during May 1998. Over
a two-week period, we monitored 52 pregnant women, out of
whom 40 were excluded from the study due to the following
reasons: 14 women were in their first trimester of pregnancy,
when hormonal changes are not as developed as in late pregnancy (11,12), 2 had fasting glucose levels above 6.66
mmol/L, 2 had glucose levels above 11.1 mmol/L after glucose
loading (indicating gestational diabetes), 5 had a history of
gastrointestinal system disorders, 1 had undergone gastrointestinal surgery, 1 had diabetes mellitus, 2 were on medication (which could have affected the release of studied hormones), 2 had abortions (excluded because of possible effects
of the cause of abortion on study parameters), and 11 refused
to volunteer. Eighteen non-pregnant women were chosen
from those who visited the Center, on the basis of the following criteria: no gastrointestinal disorders, no previous abdominal surgery or abortion, normal fasting glucose levels, normal
blood glucose levels after glucose loading (similar to the criteria applied in choosing pregnant women), and no medications. Median ages of pregnant and non-pregnant women
were 28 (range 22-35) and 26 years (range 19-38), respectively. The difference in median age between the two women
groups was not significant (Mann Whitney U-test, p=0.21).
All pregnant women had a 29-week median (range 16-36) of
gestational age.
Measurements
Before glucose loading, all subjects were allowed to perform daily physical activity and were on a 3-day diet containing at least 150 g of carbohydrates. At the end of the third day,
initial blood samples were collected from the volunteers, who
fasted overnight, to measure concentrations of glucose, gastrin, glucagon, and insulin at 0 time-point (t1). Afterwards,
glucose loading was performed by oral administration of a
single dose of 75 g glucose dissolved in flavored water. The
blood samples were collected for analysis from all volunteers
30 and 60 minutes after glucose intake (30- and 60-min
time-points).
Each patient’s blood samples were collected into two
vacutainers (one coated with ethylene-diamine tetraacetic
acid), after which the serum and plasma were promptly separated from the clot. Glucose, insulin, and gastrin concentrations were measured in serum, and glucagon was determined
in plasma. Plasma and serum were stored (6 days at longest)
at –20oC until analysis. Radioimmunoassay kits were used in
measuring insulin (DPC, Los Angeles, CA, USA), glucagon,
and gastrin concentrations (ICN Pharmaceuticals, Orangeburg, NY, USA). Serum glucose concentration was detected
by glucose oxidase method (Bayer, New York, NY, USA) on
Technicon Dax 48 autoanalyzer (Bayer, Berkeley, CA, USA).
Repective intraassay and interassay coefficients of variations
(CV) were: gastrin, 5,8%; insulin, 6,0% and 8,5%; glucagon,
6,5% and 8,0%; and glucose 2,1% and 3,0%.
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Statistics
Since the data obtained in this research did not have
normal distribution, we used non-parametric descriptive statistics – median and quartiles, instead of mean±SD. The results are presented in box-plots graphs, which show median
(the value that divides the distribution into halves) and the
first and third quartiles (the value that divides the lowest 25%
of the observations from the highest 75%, and the value that
divides the highest 25% of the observations from the lowest
75%, respectively). The Friedman test was used to calculate
the differences between concentrations in different time
points (0, 30, and 60 min) in both pregnant and non-pregnant
groups, and Bonferroni-adjusted Wilcoxon test was used to
determine which differences were significant. The differences between non-pregnant and pregnant women for each
measurement were analyzed by Mann-Whitney U-test. The
significance level was set at p<0.05. Statistical program used
was SPSS Version 9.0 for Windows Operating System.
Results
Gastrin concentration increased at 30-min
time point and decreased at 60-min time point
compared to 0 time point. The changes in serum
gastrin concentrations (Fig. 1) in different time
points (0, 30, and 60 min) were significant in the
group of non-pregnant women (Friedman’s test,
p=0.009), but not in the group of pregnant women
(Friedman’s test, p=0.264). In particular, the decrease in gastrin release from 30-min to 60-min
time point was significant in the group of
non-pregnant women (Bonferroni adjusted
Wilcoxon test, p=0.002). Gastrin value at 60-min
time point was significantly lower in non-pregnant
than in pregnant women (Mann Whitney U-test,
p=0.034).
Glucagon concentrations in pregnant women differed significantly between measurements (Friedman,
Figure 1. Changes in the levels of gastrin serum concentrations after oral ingestion of 75 g glucose (box-plots).
Bold horizontal line, median; box – bottom, 1st quartile;
box – top, 3rd quartile. Open box, gastrin level at 0 time
point; light gray box, gastrin level at 30-min time point;
dark gray box, gastrin level at 60-min time point.
Gultekin et al: Gastrin Release After Glucose Loading
Figure 2. Changes in the levels of glucagon serum concentrations after oral ingestion of 75 g glucose
(box-plots). Bold horizontal line, median; box – bottom,
1st quartile; box – top, 3rd quartile. Open box, glucagon
level at 0 time point; light gray box, glucagon level at
30-min time point; dark gray box, glucagon level at
60-min time point.
Figure 3. Changes in the levels of insulin serum concentrations after oral ingestion of 75 g glucose (box-plots).
Bold horizontal line, median; box – bottom, 1st quartile;
box – top, 3rd quartile. Open box, insulin level at 0 time
point; light gray box, insulin level at 30-min time point;
dark gray box, insulin level at 60-min time point.
Croat Med J 2001;42:151-155
Figure 4. Changes in the levels of glucose serum concentrations after oral ingestion of 75 g glucose (box-plots).
Bold horizontal line, median; box – bottom, 1st quartile;
box – top, 3rd quartile. Open box, insulin glucose level
at 0-min time point; light gray box, glucose level at
30-min time point; dark gray bars, glucose level at
60-min time point.
and 60 min) were significant in both non-pregnant
and pregnant women (Friedman’s test, p<0.001).
The increase in insulin concentrations from 0-min
time point to 60-min time point was significant in
both groups (Bonferroni-adjusted Wilcoxon test,
p<0.001), whereas the increase from 30-time point
to 60-min time point insuline concentrations was significant only in pregnant women (Bonferroni-adjusted
Wilcoxon test, p=0.002). Insulin concentration at
60-min time point was significantly lower in the group of
non-pregnant women (Mann Whitney U-test, p=0.051).
Significant changes in glucose concentrations
were observed in both groups of women (Friedman’s
test, p<0.001, Fig. 4). The increase in glucose concentrations from 0 to 30-min time point was significant in
both groups (Bonferroni-adjusted Wilcoxon test,
p<0.001), whereas the decrease in glucose concentrations from 30- to 60-min time point was significant in
non-pregnant women (Bonferroni-adjusted Wilcoxon
test, p=0.022). Glucose serum concentrations at 0
time point were significantly higher in non-pregnant
than in pregnant women (Mann Whitney U-test,
p=0.002). No significant correlation was observed between the level of gastrin and other measured parameters (glucose, glucagon, and insulin) in either group
of women.
Discussion
p=0.013), in contrast to non-pregnant women (Fig.
2).
The differences between insulin serum concentrations (Fig. 3) at three different time-points (0, 30,
In this study, the blood glucose levels and correspondent insulin levels at 30-min and 60-min
time points were significantly increased by oral
glucose loading (especially blood glucose at
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Gultekin et al: Gastrin Release After Glucose Loading
Therefore, we did not detect inhibition of gastrin release
by increased blood glucose concentration in
non-hyperglycemic women (at 30-min time point).
Findings in several studies have suggested that gastrointestinal function is affected by glucose concentration
(13-17). During acute hyperglycemia induced by intravenous glucose infusion, gastric acid secretion is reduced in
healthy subjects (2,18-21). Lam et al (2) showed that acute
hyperglycemia significantly reduced the intravenous
amino acid-stimulated acid output and gastrin release. They
also showed that meal-stimulated gastrin release was significantly reduced during hyperglycemia (22). The mechanism(s) responsible for the inhibitory effect of hyperglycemia
on gastrin release is still not known. Sakaguchi et al (23) suggested that portal glucose concentration higher than 10
mmol/L signaled or modulated gastric acid secretion controlled by gastrin. But, it was possible that hormonal
changes resulting from hyperglycemia modulated gastrointestinal function. The modulatory effect of glucose on gastrin
release can be mediated indirectly through hormonal or neural
changes secondary to changes in glucose concentration.
Previous studies have shown that high concentration of
insulin does not inhibit but, on the contrary, stimulates
acid secretion during hypoglycemia (5). However, the effect of insulin on gastrin release and acid secretion during normoglycemia or hyperglycemia is not known.
The increased insulin release and reduced glucagon
release in this study may have been caused by increased
blood glucose concentration due to 75 g oral glucose
load. However, increased level of insulin did not cause
any hypoglycemia by which gastric acid secretion could
be directly stimulated. This is contrary to the previous
studies in which intravenous administration of insulin
stimulated gastric acid secretion (4,5). Similarly, since
the inhibitory effect of glucagon on gastrin release is
achieved only during the hyperglycemia induced by
glucagon infusion (not by glucose infusion) (24), the effect of reduced serum concentration of glucagon due to
increased blood glucose concentration in our study could
not be the cause of stimulated gastrin release. This may,
therefore, indicate that increased insulin release after ingestion of glucose could not be associated with the observed stimulated gastrin release unless the level of insulin release had caused hypoglycemia (4,5). Thus, one can
speculate that in our study, unlike in previous research
(2,3), the initially increased gastrin release might be due
to the oral administration of glucose, suggesting that the
level of blood glucose was not sufficiently high to induce
hyperglycemia that would inhibit gastrin release. Our results confirm those of Sakaguchi et al (23), who showed
that gastric acid secretion controlled by gastrin could not
be inhibited unless the portal glucose concentration was
higher than 10 mmol/L. Therefore, in this case, the subsequent increase in blood glucose concentration (under
the hyperglycemic glucose values) by oral glucose loading could be the cause of increased gastrin release 30
minutes after oral glucose intake. The increased blood
insulin concentration could not stimulate gastrin release
because insulin could not initiate any increase in gastrin
levels, unless high insulin concentration had induced
hypoglycemia. However, this is only a speculation, since
the gastrin release is, in fact, controlled not only by blood
glucose concentration, but also by hormonal, metabolic,
and neural changes in the organism.
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Plasma glucagon and serum insulin concentrations
are profoundly influenced by pregnancy, since pregnancy is a state of physiologic insulin resistance compensated by an increase of insulin secretion (9). We
found glucose concentration significantly low, and insulin and glucagon concentrations significantly high in
pregnant women at 0 time point, compared with
non-pregnant women. It has been shown that insulin and
glucagon concentrations are high during pregnancy
(9,10) and that, in late pregnancy, glucose administration
causes a marked increase in peripheral insulin concentrations (11). Insulin release after a glucose load increased
more in late pregnancy than in non-pregnant state (12).
Increased insulin concentrations and/or greater consumption of glucose may explain lower glucose concentrations in pregnant women at 0 time point (t1).
In our study, gastrin concentration was increased after 30 minutes compared to 0 time point in both pregnant
and non-pregnant women. In non-pregnant women, the
gastrin release after 60 minutes decreased, compared
with 30-min time point. This appeared to be associated
with a decrease in blood glucose concentration, indicating a possible regulation of gastrin release by blood glucose concentration. However, gastrin release in pregnant
women continued to increase and was the highest at
60-min time point, irrespective of the reduction in glucose level at the same time-point. It may also be that the
blood glucose level could not affect the gastrin release in
pregnant women due to the possible metabolic and hormonal changes brought about by pregnancy.
In conclusion, the results of our study suggest that
only in hypoglycemic or hyperglycemic conditions it
would be possible to detect the mechanism of inhibition
or stimulation of gastrin release by changes in blood glucose and insulin concentrations.
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Received: September 5, 2000
Accepted: December 21, 2000
Correspondence to:
Fatih Gultekin
Department of Biochemistry and Clinical Biochemistry
School of Medicine, Suleyman Demirel University
32040 Isparta, Turkey
[email protected]
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