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Inhibition of gastric acid secretion elicited by d -glucose anomers in man
EXPERIMENTAL
NEUROLOGY
84,231-236
(1984)
RESEARCH
NOTE
Inhibition of Gastric Acid Secretion Elicited by D-Glucose Anomers in Man TAKEO SAKAGUCHI, KAZUHIRO ISHIGURO, YASUO HAYASHI, AND AKIRA HASEGAWA’ Departments of Physiology and Internal Medicine, Niigata University School of Medicine, Niigata, Niigata Shinai Hospital, Niigata, Japan Received June 23, 1983; revision received December 13, 1983 Acid outputs from the stomach were measured after venous administration of Dglucose and its optical anomers in men with insulin hypoglycemia. A significant decrease in gastric acid output was noted alter the administration of 277 mM a-~ glucose, 277 mM optically equilibrated ~-glucose consisting of 36% a-anomer and 64% @-anomer, or 277 mM @-mucose. The effect of @-~glucose was most potent in the three forms of o-glucose. NaCl solution, however, produced no appreciable change in the acid outputs. Our findings suggested that, in humans, &~-glucose in the blood may play an important role in the activation ofglucose-sensitive mechanisms controlling vagally mediated secretion of gastric acid.
It has been accepted that changes in the glucose concentration in the blood influence gastric acid secretion; hypoglycemia causes excessive secretion of gastric acid by stimulating the vagal glucose-sensitive mechanisms ( 1, 2). On the other hand, ~-glucose dissolved in an aqueous solution has been known to exist as an optically equilibrated mixture of its two anomers; 36% cr-anomer and 64% Banomer (14). Moreover, in higher animals, almost the same anomeric fraction has been shown in the blood (5, 10). However, the physiologic significance of each anomer remains to be elucidated in humans. Recently, it was observed that ~-glucose and its anomers injected into the vein differentially affected the gastric acid secretion in man. ’ The authors express their thanks to Miss T. Yamagiwa for her excellent technical assistance. K. I. is at the Niigata Shinai Hospital, Niigata and Y. H. is in Internal Medicine at Nii8ata University. Please address correspondence to T. Sakaguchi at the Department of Physiology. 231 0014-4886/84 $3.00 Copyti&t 0 1984 by Academic Press, Inc. All rights of reproduction in any form reserved.
232
SAKAGUCHI
ET AL.
Forty-five normal men (2 1 to 29 years old) weighing about 5 1 to 7 1 kg were tested. They were divided into five groups; the first group of 6 men received the sham (without injection), the second group of 7 men received NaCl, the third group of 10 men received a-D-ghCOS2, the fourth group of 10 men received equilibrated ~-glucose, and the fifth group of 10 men received &~-glucose. Different doses of NaCl and equilibrated ~-glucose were repeatedly administered to the same group. They were deprived of food for 12 h before each experiment and the experiments were conducted in the mornings to eliminate any diurnal variation in plasma concentrations of glucose and insulin (9). The experimental preparation for gastric acid estimation was based fundamentally on the methods described earlier (8). Briefly, a Salem Sump Tube (Argyle, Japan) was introduced into the stomach through the esophagus and was fixed in position with a tape on the lip. Before collection of the gastric juice, residual food particles in the stomach were washed out with warm saline. Gastric juice was then actively taken up with a pump (Pharmacia, Sweden) into a collecting tube. The pressure of suction was about 30 mm Hg and as the gastric juice was collected in the tube, the volume of each sample was measured and titratable acidity (end point pH 7.0) was determined using N/100 NaOH. With this system, the acid output was calculated every 15 min. Throughout the experiment, the body temperature of each man was between 36.5 to 368°C. The D-glucose and NaCl dissolved in distilled water kept at 25°C were infused through a catheter placed in a vein in the forearm. The purity of alpha and beta anomers (Nakarai, Japan) was more than 96%. Optically equilibrated ~-glucose solution consisting of 36% a-D-glucose and 64% jf?-D-&COSe was obtained by incubating at room temperature (22’C) either (Y- or @-D-glucose solution for 24 h to induce the glucose to mutarotate completely. Alpha and beta anomers of crystallized ~-glucose were dissolved in water at 25°C immediately before use to eliminate mutarotation of the glucose. It was preliminarily estimated using a digital polarimeter (JASCO, Japan) that the time periods required for the two anomers to be dissolved in the same water were about 15 s and the mutarotational half-life of the two anomers was 26.1 + 0.5 min (N = 5) at 25°C in the same water. From the mutarotational aspect, a venous injection (250 ml) of test solutions was determined at 15 min. Regular insulin (Novo, Denmark) was administered i.v. (0.2 U/kg) to stimulate basal secretion of gastric acid (8). The concentrations of glucose and insulin in the blood were measured by the methods reported earlier ( 19, 20). Blood for glucose and insulin estimation was drawn through the same catheter in the vein. Statistical significance of differences between values was determined by paired t test; P < 0.05 was taken as indicative of a significance between means.
GASTRIC
ACID SECRETION
BY D-GLUCOSE
ANOMERS
233
When gastric acid outputs were estimated every 15 min, the 0.2-U/kg insulin injections produced a gradual elevation in the acid output for 30 to 60 min which was followed by a gradual decrease lasting about 30 min (Fig. 1). On the basis of that finding, venous blood tests were always begun about 45 min after the insulin injection. The concentrations of acid output just before and 30 min after administering the sham test, 154 mM NaCl, or 277 mM equilibrated ~-glucose were not significantly different from each other. The concentration of acid output 15 min after administering the ~-glucose was significantly (P < 0.02) less than that 15 min after administering the sham or NaCl (Fig. 1). Equilibrated ~-glucose solutions ( 138,277, and 4 16 mM) were administered in the vein to enable the acid responses to be examined at three different blood glucose concentrations (Fig. 2). Although the 138 m.M ~-glucose administration failed to cause a response, the 277 and 416 m.M ~-glucose administrations produced a significant decrease (P < 0.05 and P -K 0.02, respectively) in the acid outputs relative to the concentration before injection. Plasma concentrations of glucose before, and 30 min after administering the three doses of ~-glucose were not significantly different from each other. However, the concentrations of ghrcose 15 min after the 277 and 416 rnM ~-glucose administrations increased significantly (P < 0.05 and P < 0.01) compared with the concentration before injection. The 308 m.M NaCl administration produced no appreciable change in acid output and glucose concentration. Plasma concentration (mean + SE) of insulin just before the venous test administration was 403 f 9 (N = 45) pM (Fig. 2).
FIG. 1. Time course of concentrations of gastric acid output atIer administering 0.2 U/kg insulin (0: N = 6). A gradual elevation in gastric acid output was noted 30 to 60 min after the insulin injection. NaCl(154 mM) (X: N = 7) and equilibrated D-glucose (277 mM) (0: N = 10) were injected, i.v., 45 min after administration of insulin. Arrows represent the time of the insulin injections (I) or the duration of NaCl and equilibrated ~glucose injections (II). Values are means f SE. The enhanced concentrations of gastric acid output caused by the insulin injection were transiently suppressed after administration of ~glucose.
234
SAKAGUCHI
5.0
ET AL.
c
al AAvV
+
A
..* V
AA*o
hA+o
1
0' 0
15
30
45 (mini
FIG. 2. The effect of venous injections of 138 (AZ N = lo), 277 (A: N = IO), and 416 (W: N = 10) mM equilibrated ~glucose, and 308 mM NaCI (V: N = 7) on the acid output provoked by 0.2 U/kg insulin. Horizontal bar shows duration of the venous injection. Values are means + SE. *P < 0.05, **P c 0.02, and ***P < 0.0 1: significantly different from the value just before injection.
The concentrations (mean -t SE) of gastric acid output 15 min after administering the sham, 277 mit4 &D&tCOSe, 277 mM equilibrated D-glucose, or 277 mM j3-~-glucose were 2.80 ? 0.31 (N = 6), 2.16 + 0.16 (N = lo), 2.01 f 0.17 (N = lo), and 1.64 + 0.15 (N = 10) meq/l5 min, respectively (Fig. 3). The concentrations of the acid output after administering the three forms of D-glucose decreased significantly (P < 0.02-0.005) compared with the concentration after administration of the sham. The /3-~-glucose seemed to produce a further reduction in the acid outputs; this reduction was greatest in the three forms of ~-glucose solution. Although elevated secretion of gastric acid evoked by insulin has been shown to be depressed vagally by glucose (1, 2, 6, 18), only a few researchers have reported the relation between gastric acid output and the concentration of glucose in the blood during insulin-hypoglycemia (7). In the present study, the three different doses of equilibrated ~-glucose injected into the vein appeared to induce a dose-dependent reduction in acid output (Figs. 1 and 2); we conclude that increasing the concentration of glucose in the blood consistently inhibits the raised gastric acid output. The inhibitory response produced by the ~-glucose solutions was not reproduced by hypertonic NaCl solutions (Fig. 2), suggesting that the response is not due to osmotic effects. However, the action site of ~-glucose on the acid response is not simple to explain. Because glucose-sensitive mechanisms vagally controlling gastric acid secretion have been well documented in the central nervous regions (2) and in the hepatic portal regions (15), the inhibitory responses observed are thus derived from a mechanism in the brain or the hepatic portal vein or from both. Unfortunately, the present data did not shed light on this problem.
GASTRIC
ACID SECRETION
BY D-GLUCOSE
ANOMERS
235
FIG. 3. The concentrations of gastric acid output 15 min after administering the sham (I), 277 mM a-~-glucose (II), 277 m&f equilibrated ~glucose (III), or 277 m44 j3-~-glucose (IV). Values are means + SE. Numbers in parentheses represent the number of men examined. a, P < 0.02 vs. sham; b, P < 0.005 vs. sham; c, P < 0.05 vs. the a-Dglucose or the equilibrated 5glucose.
Although there have heen numerous investigations of the uptake and utilization of ~glucose, only a few reports have dealt with the uptake and utilization of a- and B-D-glucose. It has been rather difficult to study the physiologic significance of cy- and @anomers of ~-glucose because of the rapid mutarotation of the two anomers. In the present study, mutarotational half-life of the two anomers in distilled water kept at 25°C was about 27 min, however, a venous administration of ~-glucose anomers was completed in 15 min. Therefore, in view of this mutarotation, this experimental model provides a tool for the study of the possible physiologic function of the glucose anomers, though mutarotational half-life of the two anomers in whole blood was found to be 2.3 min at 37°C in man (unpublished data). Concerning the physiologic function of ~glucose anomers, several works have suggested that /3-~-glucose is more rapidly transported and metabolized by various cells and tissues than a-~-glucose (3, 4, 11-13, 15-17). In the present experiment, @-~-glucose was most potent in reducing the gastric acid outputs (Fig. 3); anomeric preference is expected to be valid in the vagal mechanism detecting glucose. Although more definitive experiments are needed to determine the exact action site of anomeric predominancy, the present data suggest that /3-Dglucose in the blood may play an important role in activating the mechanisms vagally controlling gastric acid secretion in man. REFERENCES 1. BROOKS, F. P. 1967. Central neural control of acid secretion. Pages 805-826 in C. F. CODE AND W. HEIDEL, Eds., Handbook ofPhysiology, Sect. 6. Williams & Wilkins, Baltimore. 2. COLIN-JONES, D. G., ANLI R. L. HIMSWORTH. 1970. The location of the chemorcceptor
236
SAKAGUCHI
ET AL.
controlling gastric acid secretion during hypoglycaemia. J. Physiol. (London) 206: 397409. 3. FAUST, R. G. 1960. Monosaccharide penetration into human red blood cells by an altered dilfusion mechanism. J. Cell. Comp. Physiol. 56: 103-121. 4. FISHMAN, P. H., AND J. M. BAILEY. 1974. Mutarotases X. Anomer specific glucose transport in ascites tumor cells. Am. J. Physiol. 226: 1007-1014. 5. HILL, J. B., AND D. S. COWART. 1967. Mutsrotase and glucose anomers. Biochem. Med. 1: 62-79.
6. HIRANO, T., AND A. NIIJIMA. 1980. Effects of 2deoxy-D-glucose, glucose and insulin on efferent activity in gastric vagus nerve. Experientiu 36: 1197-1198. 7. HIRSCHOWITZ, B. I. 1967. Continuing gastric secretion after insulin hypoglycemia despite glucose injection. Am. J. Dig. Dis. 12: 19-25. 8. HOLLANDER, F. 1946. The insulin test for the presence of intact nerve fibers after vagal operations for peptic ulcer. Gustroenterofogy 7: 607-6 14. 9. JARRET~, R. J. 1979. Rhythms in insulin and glucose. Pages 247-258. in D. T. KRIEGER, Ed., Endocrine Rhythms. Raven Press, New York. 10. MIWA, I,, K. MAEDA, AND J. OKUDA. 1978. Anomeric compositions of @ucose in tissues and blood of rat. Experientia 34: 167-169. 11. MIWA, I., J. OKUDA, H. NIKI, AND A. NIKI. 1975. Uptake of radioactive ~-glucose anomers by pancreatic islets. J. Biochem. 78: 1109-l 111. 12. NAGATA, Y., T. NANBA, M. ANDO, I. MIWA, AND J. OKUDA. 1979. Anomeric preferences of ~-glucose uptake and utilization by cerebral cortex slices of rats. Neurochem. Res. 4: 505-5 16.
13. OKUDA, J., I. MIWA, M. SATO, AND T. MURATA. 1977. Uptake of ~-glucose anomers by rat retina. Experientia 33: 19-20. 14. PIGMAN, W., AND H. S. ISBELL. 1968. Mutarotation of sugars in solution. Adv. Curbohydr. Chem. Biochem. 23: 11-57. 15. SAKAGUCHI, T. 1982. Alterations in gastric acid secretion following hepatic portal injections of ~-glucose and its anomers. J. Auton. Nerv. Syst. 5: 337-344, 16. SAKAGUCHI, T., AND M. IWANAGA. 1982. Effects of D-glucose anomers on afferent discharge in the hepatic vagus nerve. Experientia 38: 475-476. 17. SAKAGUCHI, T., T. TAGUCHI, AND J. OKUDA. 1983. Different effectsof ~glucose anomers on enhanced motility of the stomach. Biochem. Int. 7: 299-305. 18. SAKAGUCHI, T., AND K. YAMAGUCHI. 1979. Changes in efferent activities of the gastric vagus nerve by administration of glucose in the portal vein. Experientia 35: 875-876. 19. SAKAGUCHI, T., AND K. YAMAGUCHI. 1980. Effects of vagal stimulation, vagotomy and adrenslectomy on release of insulin in the ret. J. Endocrinol. 85: 131-136. 20. SALOMON, L. L., AND J. E. JOHNSON. 1959. Enzymatic microdetermination of glucose in blood and urine. Anal. Chem. 31: 453-456.
NEUROLOGY
84,231-236
(1984)
RESEARCH
NOTE
Inhibition of Gastric Acid Secretion Elicited by D-Glucose Anomers in Man TAKEO SAKAGUCHI, KAZUHIRO ISHIGURO, YASUO HAYASHI, AND AKIRA HASEGAWA’ Departments of Physiology and Internal Medicine, Niigata University School of Medicine, Niigata, Niigata Shinai Hospital, Niigata, Japan Received June 23, 1983; revision received December 13, 1983 Acid outputs from the stomach were measured after venous administration of Dglucose and its optical anomers in men with insulin hypoglycemia. A significant decrease in gastric acid output was noted alter the administration of 277 mM a-~ glucose, 277 mM optically equilibrated ~-glucose consisting of 36% a-anomer and 64% @-anomer, or 277 mM @-mucose. The effect of @-~glucose was most potent in the three forms of o-glucose. NaCl solution, however, produced no appreciable change in the acid outputs. Our findings suggested that, in humans, &~-glucose in the blood may play an important role in the activation ofglucose-sensitive mechanisms controlling vagally mediated secretion of gastric acid.
It has been accepted that changes in the glucose concentration in the blood influence gastric acid secretion; hypoglycemia causes excessive secretion of gastric acid by stimulating the vagal glucose-sensitive mechanisms ( 1, 2). On the other hand, ~-glucose dissolved in an aqueous solution has been known to exist as an optically equilibrated mixture of its two anomers; 36% cr-anomer and 64% Banomer (14). Moreover, in higher animals, almost the same anomeric fraction has been shown in the blood (5, 10). However, the physiologic significance of each anomer remains to be elucidated in humans. Recently, it was observed that ~-glucose and its anomers injected into the vein differentially affected the gastric acid secretion in man. ’ The authors express their thanks to Miss T. Yamagiwa for her excellent technical assistance. K. I. is at the Niigata Shinai Hospital, Niigata and Y. H. is in Internal Medicine at Nii8ata University. Please address correspondence to T. Sakaguchi at the Department of Physiology. 231 0014-4886/84 $3.00 Copyti&t 0 1984 by Academic Press, Inc. All rights of reproduction in any form reserved.
232
SAKAGUCHI
ET AL.
Forty-five normal men (2 1 to 29 years old) weighing about 5 1 to 7 1 kg were tested. They were divided into five groups; the first group of 6 men received the sham (without injection), the second group of 7 men received NaCl, the third group of 10 men received a-D-ghCOS2, the fourth group of 10 men received equilibrated ~-glucose, and the fifth group of 10 men received &~-glucose. Different doses of NaCl and equilibrated ~-glucose were repeatedly administered to the same group. They were deprived of food for 12 h before each experiment and the experiments were conducted in the mornings to eliminate any diurnal variation in plasma concentrations of glucose and insulin (9). The experimental preparation for gastric acid estimation was based fundamentally on the methods described earlier (8). Briefly, a Salem Sump Tube (Argyle, Japan) was introduced into the stomach through the esophagus and was fixed in position with a tape on the lip. Before collection of the gastric juice, residual food particles in the stomach were washed out with warm saline. Gastric juice was then actively taken up with a pump (Pharmacia, Sweden) into a collecting tube. The pressure of suction was about 30 mm Hg and as the gastric juice was collected in the tube, the volume of each sample was measured and titratable acidity (end point pH 7.0) was determined using N/100 NaOH. With this system, the acid output was calculated every 15 min. Throughout the experiment, the body temperature of each man was between 36.5 to 368°C. The D-glucose and NaCl dissolved in distilled water kept at 25°C were infused through a catheter placed in a vein in the forearm. The purity of alpha and beta anomers (Nakarai, Japan) was more than 96%. Optically equilibrated ~-glucose solution consisting of 36% a-D-glucose and 64% jf?-D-&COSe was obtained by incubating at room temperature (22’C) either (Y- or @-D-glucose solution for 24 h to induce the glucose to mutarotate completely. Alpha and beta anomers of crystallized ~-glucose were dissolved in water at 25°C immediately before use to eliminate mutarotation of the glucose. It was preliminarily estimated using a digital polarimeter (JASCO, Japan) that the time periods required for the two anomers to be dissolved in the same water were about 15 s and the mutarotational half-life of the two anomers was 26.1 + 0.5 min (N = 5) at 25°C in the same water. From the mutarotational aspect, a venous injection (250 ml) of test solutions was determined at 15 min. Regular insulin (Novo, Denmark) was administered i.v. (0.2 U/kg) to stimulate basal secretion of gastric acid (8). The concentrations of glucose and insulin in the blood were measured by the methods reported earlier ( 19, 20). Blood for glucose and insulin estimation was drawn through the same catheter in the vein. Statistical significance of differences between values was determined by paired t test; P < 0.05 was taken as indicative of a significance between means.
GASTRIC
ACID SECRETION
BY D-GLUCOSE
ANOMERS
233
When gastric acid outputs were estimated every 15 min, the 0.2-U/kg insulin injections produced a gradual elevation in the acid output for 30 to 60 min which was followed by a gradual decrease lasting about 30 min (Fig. 1). On the basis of that finding, venous blood tests were always begun about 45 min after the insulin injection. The concentrations of acid output just before and 30 min after administering the sham test, 154 mM NaCl, or 277 mM equilibrated ~-glucose were not significantly different from each other. The concentration of acid output 15 min after administering the ~-glucose was significantly (P < 0.02) less than that 15 min after administering the sham or NaCl (Fig. 1). Equilibrated ~-glucose solutions ( 138,277, and 4 16 mM) were administered in the vein to enable the acid responses to be examined at three different blood glucose concentrations (Fig. 2). Although the 138 m.M ~-glucose administration failed to cause a response, the 277 and 416 m.M ~-glucose administrations produced a significant decrease (P < 0.05 and P -K 0.02, respectively) in the acid outputs relative to the concentration before injection. Plasma concentrations of glucose before, and 30 min after administering the three doses of ~-glucose were not significantly different from each other. However, the concentrations of ghrcose 15 min after the 277 and 416 rnM ~-glucose administrations increased significantly (P < 0.05 and P < 0.01) compared with the concentration before injection. The 308 m.M NaCl administration produced no appreciable change in acid output and glucose concentration. Plasma concentration (mean + SE) of insulin just before the venous test administration was 403 f 9 (N = 45) pM (Fig. 2).
FIG. 1. Time course of concentrations of gastric acid output atIer administering 0.2 U/kg insulin (0: N = 6). A gradual elevation in gastric acid output was noted 30 to 60 min after the insulin injection. NaCl(154 mM) (X: N = 7) and equilibrated D-glucose (277 mM) (0: N = 10) were injected, i.v., 45 min after administration of insulin. Arrows represent the time of the insulin injections (I) or the duration of NaCl and equilibrated ~glucose injections (II). Values are means f SE. The enhanced concentrations of gastric acid output caused by the insulin injection were transiently suppressed after administration of ~glucose.
234
SAKAGUCHI
5.0
ET AL.
c
al AAvV
+
A
..* V
AA*o
hA+o
1
0' 0
15
30
45 (mini
FIG. 2. The effect of venous injections of 138 (AZ N = lo), 277 (A: N = IO), and 416 (W: N = 10) mM equilibrated ~glucose, and 308 mM NaCI (V: N = 7) on the acid output provoked by 0.2 U/kg insulin. Horizontal bar shows duration of the venous injection. Values are means + SE. *P < 0.05, **P c 0.02, and ***P < 0.0 1: significantly different from the value just before injection.
The concentrations (mean -t SE) of gastric acid output 15 min after administering the sham, 277 mit4 &D&tCOSe, 277 mM equilibrated D-glucose, or 277 mM j3-~-glucose were 2.80 ? 0.31 (N = 6), 2.16 + 0.16 (N = lo), 2.01 f 0.17 (N = lo), and 1.64 + 0.15 (N = 10) meq/l5 min, respectively (Fig. 3). The concentrations of the acid output after administering the three forms of D-glucose decreased significantly (P < 0.02-0.005) compared with the concentration after administration of the sham. The /3-~-glucose seemed to produce a further reduction in the acid outputs; this reduction was greatest in the three forms of ~-glucose solution. Although elevated secretion of gastric acid evoked by insulin has been shown to be depressed vagally by glucose (1, 2, 6, 18), only a few researchers have reported the relation between gastric acid output and the concentration of glucose in the blood during insulin-hypoglycemia (7). In the present study, the three different doses of equilibrated ~-glucose injected into the vein appeared to induce a dose-dependent reduction in acid output (Figs. 1 and 2); we conclude that increasing the concentration of glucose in the blood consistently inhibits the raised gastric acid output. The inhibitory response produced by the ~-glucose solutions was not reproduced by hypertonic NaCl solutions (Fig. 2), suggesting that the response is not due to osmotic effects. However, the action site of ~-glucose on the acid response is not simple to explain. Because glucose-sensitive mechanisms vagally controlling gastric acid secretion have been well documented in the central nervous regions (2) and in the hepatic portal regions (15), the inhibitory responses observed are thus derived from a mechanism in the brain or the hepatic portal vein or from both. Unfortunately, the present data did not shed light on this problem.
GASTRIC
ACID SECRETION
BY D-GLUCOSE
ANOMERS
235
FIG. 3. The concentrations of gastric acid output 15 min after administering the sham (I), 277 mM a-~-glucose (II), 277 m&f equilibrated ~glucose (III), or 277 m44 j3-~-glucose (IV). Values are means + SE. Numbers in parentheses represent the number of men examined. a, P < 0.02 vs. sham; b, P < 0.005 vs. sham; c, P < 0.05 vs. the a-Dglucose or the equilibrated 5glucose.
Although there have heen numerous investigations of the uptake and utilization of ~glucose, only a few reports have dealt with the uptake and utilization of a- and B-D-glucose. It has been rather difficult to study the physiologic significance of cy- and @anomers of ~-glucose because of the rapid mutarotation of the two anomers. In the present study, mutarotational half-life of the two anomers in distilled water kept at 25°C was about 27 min, however, a venous administration of ~-glucose anomers was completed in 15 min. Therefore, in view of this mutarotation, this experimental model provides a tool for the study of the possible physiologic function of the glucose anomers, though mutarotational half-life of the two anomers in whole blood was found to be 2.3 min at 37°C in man (unpublished data). Concerning the physiologic function of ~glucose anomers, several works have suggested that /3-~-glucose is more rapidly transported and metabolized by various cells and tissues than a-~-glucose (3, 4, 11-13, 15-17). In the present experiment, @-~-glucose was most potent in reducing the gastric acid outputs (Fig. 3); anomeric preference is expected to be valid in the vagal mechanism detecting glucose. Although more definitive experiments are needed to determine the exact action site of anomeric predominancy, the present data suggest that /3-Dglucose in the blood may play an important role in activating the mechanisms vagally controlling gastric acid secretion in man. REFERENCES 1. BROOKS, F. P. 1967. Central neural control of acid secretion. Pages 805-826 in C. F. CODE AND W. HEIDEL, Eds., Handbook ofPhysiology, Sect. 6. Williams & Wilkins, Baltimore. 2. COLIN-JONES, D. G., ANLI R. L. HIMSWORTH. 1970. The location of the chemorcceptor
236
SAKAGUCHI
ET AL.
controlling gastric acid secretion during hypoglycaemia. J. Physiol. (London) 206: 397409. 3. FAUST, R. G. 1960. Monosaccharide penetration into human red blood cells by an altered dilfusion mechanism. J. Cell. Comp. Physiol. 56: 103-121. 4. FISHMAN, P. H., AND J. M. BAILEY. 1974. Mutarotases X. Anomer specific glucose transport in ascites tumor cells. Am. J. Physiol. 226: 1007-1014. 5. HILL, J. B., AND D. S. COWART. 1967. Mutsrotase and glucose anomers. Biochem. Med. 1: 62-79.
6. HIRANO, T., AND A. NIIJIMA. 1980. Effects of 2deoxy-D-glucose, glucose and insulin on efferent activity in gastric vagus nerve. Experientiu 36: 1197-1198. 7. HIRSCHOWITZ, B. I. 1967. Continuing gastric secretion after insulin hypoglycemia despite glucose injection. Am. J. Dig. Dis. 12: 19-25. 8. HOLLANDER, F. 1946. The insulin test for the presence of intact nerve fibers after vagal operations for peptic ulcer. Gustroenterofogy 7: 607-6 14. 9. JARRET~, R. J. 1979. Rhythms in insulin and glucose. Pages 247-258. in D. T. KRIEGER, Ed., Endocrine Rhythms. Raven Press, New York. 10. MIWA, I,, K. MAEDA, AND J. OKUDA. 1978. Anomeric compositions of @ucose in tissues and blood of rat. Experientia 34: 167-169. 11. MIWA, I., J. OKUDA, H. NIKI, AND A. NIKI. 1975. Uptake of radioactive ~-glucose anomers by pancreatic islets. J. Biochem. 78: 1109-l 111. 12. NAGATA, Y., T. NANBA, M. ANDO, I. MIWA, AND J. OKUDA. 1979. Anomeric preferences of ~-glucose uptake and utilization by cerebral cortex slices of rats. Neurochem. Res. 4: 505-5 16.
13. OKUDA, J., I. MIWA, M. SATO, AND T. MURATA. 1977. Uptake of ~-glucose anomers by rat retina. Experientia 33: 19-20. 14. PIGMAN, W., AND H. S. ISBELL. 1968. Mutarotation of sugars in solution. Adv. Curbohydr. Chem. Biochem. 23: 11-57. 15. SAKAGUCHI, T. 1982. Alterations in gastric acid secretion following hepatic portal injections of ~-glucose and its anomers. J. Auton. Nerv. Syst. 5: 337-344, 16. SAKAGUCHI, T., AND M. IWANAGA. 1982. Effects of D-glucose anomers on afferent discharge in the hepatic vagus nerve. Experientia 38: 475-476. 17. SAKAGUCHI, T., T. TAGUCHI, AND J. OKUDA. 1983. Different effectsof ~glucose anomers on enhanced motility of the stomach. Biochem. Int. 7: 299-305. 18. SAKAGUCHI, T., AND K. YAMAGUCHI. 1979. Changes in efferent activities of the gastric vagus nerve by administration of glucose in the portal vein. Experientia 35: 875-876. 19. SAKAGUCHI, T., AND K. YAMAGUCHI. 1980. Effects of vagal stimulation, vagotomy and adrenslectomy on release of insulin in the ret. J. Endocrinol. 85: 131-136. 20. SALOMON, L. L., AND J. E. JOHNSON. 1959. Enzymatic microdetermination of glucose in blood and urine. Anal. Chem. 31: 453-456.