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Biomedical subjects

M Otsuki

Publications and source records attributed to M Otsuki.

At least 307 records · Page 17Linked to original sources
PubMed1981

Effect of alpha-glucosidase inhibitor on human pancreatic and salivary alpha-amylase.

The mode of inhibition of a new complex oligosaccharide that inhibits the alpha-glucoside hydrolase activity of pancreatic and salivary alpha-amylase was studied. Kinetic analysis revealed a non-competitive type of inhibition with a Ki of 1.47 +/- 0.03 micrograms when tested against human pancreatic alpha-amylase and 3.89 +/- 0.08 micrograms against human salivary alpha-amylase. The inhibitory action of alpha-glucoside hydrolase inhibitor (alpha-GHI) on pancreatic amylase was observed over a wide range of pH (6.0--7.9), whereas the inhibition of salivary amylase was optimal at pH 6.5. Column chromatographic investigations suggested the possible formation of an enzyme-inhibitor complex because the mixture of alpha-GHI and pancreatic alpha-amylase was eluted as a single component through a Sephadex G200 column. However, this enzyme-inhibitor complex was easily separated into each component and the enzyme activity was fully recovered after electrophoresis.

Amylases↗
PubMed1981

Pancreatic exocrine secretion and immunoreactive secretin release after intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane and HCl in rats.

Portal plasma immunoreactive secretin (IRS) concentrations, pancreatic juice flow, and amylase output were simultaneously measured in response to intraduodenal infusion of 1-phenyl-1-hydroxy-n-pentane (PHP), as well as infusion of hydrochloric acid (HCl). These data were compared with those obtained from intravenous bolus injections of synthetic porcine secretin in anesthetized rats. The intraduodenal infusion of PHP or HCl at a rate of 2 ml/min for 2 min produced a dose-related increase in portal plasma secretin concentrations, pancreatic juice flow, and amylase output. However, the mechanism of secretin release by PHP seems to differ from that of HCl. The secretin response to 0.1 N HCl infused at a rate of 0.1 ml/min for 30 min was complete after 10 min, despite continued infusion, while PHP stimulated a secretin release which persisted for 10 min after cessation of infusion. The pH in the second portion of the duodenum, following PHP infusion, remained consistently greater than 6.3. PHP-stimulated pancreatic exocrine secretions were only partially suppressed by somatostatin, while secretin release was almost completely inhibited. However, intraduodenal PHP may stimulate the release of secretin along with other gastrointestinal hormones, and the endogenous release of these hormones may not be inhibited by somatostatin.

Amylases↗
PubMed1981

Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure.

Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.

Amylases↗
PubMed1981

Effect of intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane on pancreatic exocrine secretions and immunoreactive secretion release in the rat.

Pancreatic juice flow and amylase output, and the concentrations of immunoreactive secretin in portal and peripheral blood were simultaneously determined in anesthetized rats in response to intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane (PHP), a phenyl carbinol derivative induced from one of the constituents of Curcuma. PHP stimulated both pancreatic juice flow and amylase output and increased portal and jugular plasma secretin levels in a dose-related fashion. During intraduodenal instillation of PHP the pH in the second portion of the duodenum remained consistently above 6.3. Infusion of cyclic somatostatin at a dose of 5 microgram/kg/h significantly suppressed the PHP-induced secretin release, though pancreatic flow rate and amylase output were only slightly and insignificantly suppressed. These observations suggest that PHP release secretin by an acid independent mechanism but also stimulates the exocrine pancreas by a mechanism independent of secretin.

Amylases↗
PubMed1981

Effects of porcine secretin on exocrine and endocrine function in the isolated perfused rat pancreas.

The effects of both synthetic and pure natural porcine secretin on immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) release and on pancreatic exocrine secretion were studied in the isolated perfused rat pancreas. Synthetic porcine secretin stimulated a significant increase in pancreatic juice flow and amylase output at concentrations as low as 0.01 and 0.1 ng/ml, respectively. The maximal peak rate of both juice flow and amylase output was observed at 1 microgram/ml synthetic secretin. Synthetic secretin at concentrations up to 2 micrograms/ml and pure natural porcine secretin at a concentration of 1 clinical unit/ml had no effect on IRI secretion regardless of the glucose concentration (50, 100, or 150 mg/100 ml) in the perfusate. Both types of secretin, however, elicited a concentration-dependent increase in IRG secretion in the presence of 50 mg/100 ml glucose. The lowest synthetic secretin concentration causing a significant increase in IRG release was 0.1 ng/ml, and maximal stimulation was observed at 1 microgram/ml. These concentrations were similar to those eliciting minimal and maximal amylase release. Thus, synthetic and pure natural porcine secretin have been shown to not only stimulate pancreatic juice flow and amylase secretion but also to elicit IRG release from the isolated perfused rat pancreas.

Amylases↗
PubMed1981

Insulin release from the isolated perfused rat pancreas containing insulinomata induced by streptozotocin and nicotinamide: effects of glucose and responses to tumor removal.

The kinetics of insulin secretion in response to glucose were studied in the in vitro perfused rat pancreas before and after removal of islet cell tumors induced by streptozotocin and nicotinamide. In addition, insulin secretion before and after tumor removal was compared with that from normal pancreata before and after sham operations, respectively. Thus, the two pancreas preparations were subjected to repeated perfusions with glucose. Perfusion of pancreata containing tumors with 8.4 mM glucose resulted in biphasic release in a pattern similar to that of normal pancreas. However, both basal and stimulated insulin secretion of tumor-bearing pancreata were greater than either those of pancreata from which tumors had been excluded by ligature or those of normal pancreata before sham operation. A second increase in the concentration of glucose from 2.8 to 8.4 mM also produced a biphasic release of insulin from extratumoral pancreata as well as from sham-operated normal pancreata. However, the insulin secretory response to glucose of extratumoral pancreatic tissue was less than that of control pancreatic tissue. Our findings indicate that pancreatic islet cell tumors induced by streptozotocin and nicotinamide respond to glucose with typical biphasic insulin release. Thus, chemically induced rat insulinomata may provide a readily available and valuable model of insulin-secreting tissue, analogous to normal islets. Furthermore, our study suggests that the B cell function of pancreata containing tumors is inhibited by the preexisting tumor-induced hyperinsulinism or by its metabolic consequences.

Adenoma, Islet Cell↗
PubMed1981

Synergistic effect of cephalexin with mecillinam.

In vitro and in vivo synergistic effects of cephalexin and mecillinam against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens and Proteus sp. were demonstrated and their action mechanism were also discussed. The growth curve after the exposure of cephalexin and mecillinam at the concentrations at which these antibiotics had no effects when given alone showed a decreased of the turbidity and the presence of a bactericidal effect. In experimental infection in mice, the combination of both drugs showed a synergistic effect and excellent therapeutic effect. The blood concentration ratio of cephalexin to mecillinam was coincident with the concentration ratio of these antibiotics at which the synergistic effect was observed in vitro. Phase-contrast and scanning electron somewhat elongated bacteria and formation of spindle cells with swelling in the central part. A leakage of the cellular contents from part of the swelled cell wall was observed by transmission electron microscope. Cephalexin showed an affinity for penicillin binding proteins (PBPs)-1a and 3 in Escherichia coli and mecillinam showed an affinity for PBP-2. When these antibiotics were used concurrently, they exerted an additive effect to increase the affinity for PBPs. The lytic activity was increased much more after the combination of two antibiotics than after a single exposure.

Amdinocillin↗
PubMed1980

Effect of somatostatin and calcium deprivation on cholecystokinin or caerulein-induced insulin and glucagon release from the isolated perfused rat pancreas.

The present experiments were undertaken to investigate the effect of alteration in on extracellular calcium concentration and of somatostatin on cholecystokinin-(CCK)- and caerulein-induced insulin and glucagon release from the isolated perfused rat pancreas. In control studies using perfusate containing 2.5 mM CaCl2 and 50 mg/dl glucose, CCK and caerulein caused insulin and glucagon release in a dose-related fashion. During perfusion with calcium free medium, insulin release was markedly inhibited. Subsequent introduction of 2.5 mM CaCl2 to the medium restored insulin response toward control levels. Extracellular calcium depletion, however, had no effect on CCK- or caerulein-induced glucagon release. The output of glucagon in the absence of calcium was comparable to that seen in the control experiments. On the other hand, somatostatin abolished the increase in glucagon secretion, but not the increase in insulin secretion, when perfused simultaneously with CCK or caerulein. However, pretreatment for 10 min with somatostatin blocked even insulin secretion. However, pretreatment for 10 min with somatostatin blocked even insulin secretion. The effects of somatostatin on hormonal discharge are suggested to be related to an alteration in the handling of or response to calcium. Recently, somatostatin has also been shown to inhibit calcium uptake by islets. Thus, the present results indicate a differential sensitivity of CCK- and caerulein-stimulated alpha and beta cell to extracellular calcium depletion and to the effect of somatostatin.

Animals↗
PubMed1979

Discrepancies between the doses of cholecystokinin or caerulein-stimulating exocrine and endocrine responses in perfused isolated rat pancreas.

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.

Amylases↗
PubMed1979

Effect of caerulein on exocrine and endocrine pancreas in the rat.

The secretion of insulin, glucagon, pancreatic juice, and amylase in response to a 20-min iv infusion of synthetic caerulein were studied simultaneously in the anesthetized rat. Caerulein, a chemical analogue of cholecystokinin, was used in doses of 1-1000 ng/kg.min. The maximum stimulatory effect of caerulein on pancreatic juice volume and amylase output was obtained with doses of 10 ng/kg.min. With increasing doses, the effect decreased progressively. On the other hand, the release of insulin and glucagon was stimulated only by supramaximal doses of caerulein, which had little or no effect on pancreatic exocrine secretions. These results raised the question of whether, under physiological conditions, cholecystokinin regulates the secretory activity of the endocrine pancreas.

Amylases↗