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Biomedical subjects

S Kadowaki

Publications and source records attributed to S Kadowaki.

At least 55 records · Page 3Linked to original sources
PubMed1990

Activation of PKC inhibits NaF-induced inositol phospholipid turnover in rat insulinoma cells.

An investigation was done to elucidate the regulatory role of protein kinase C (PKC) in insulin release and also the effects of PKC activation on NaF-induced inositol phospholipid (PI) turnover in and insulin release from rat insulinoma cells (RINr). NaF stimulated insulin secretion in association with an increase in [3H]inositol phosphate formation in RINr cells. Furthermore, NaF induced a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-diphosphate (PIP2) with a concomitant increase of [32P]phosphatidic acid in prelabeled cells. In contrast, NaF had no effect on cyclic AMP production. Although phorbol 12,13-dibutyrate (PDBu) also stimulated insulin release, on concomitant administration of NaF and PDBu, insulin secretion was clearly less than that expected on the basis of an additive action. Moreover, PDBu significantly inhibited NaF-enhanced PI turnover. However, this inhibition was abolished after downregulating PKC by pretreating RINr cells with PDBu. Thus NaF-induced insulin release from RINr cells appears to involve enhancement of PI turnover. Moreover, because NaF is known to activate guanine nucleotide binding proteins (G proteins) directly, PKC activation appears to induce a mechanism that inhibits stimulus-secretion coupling at a level between G protein and phospholipase C-induced PIP2 hydrolysis.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo.

The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver.

Animals↗
PubMed1990

Purification and characterization of a novel fungal endo-beta-N-acetylglucosaminidase acting on complex oligosaccharides of glycoproteins.

A novel endo-beta-N-acetylglucosaminidase acting on complex type sugar chains of glycoproteins was found in the culture broth of a fungus isolated from soil and identified as Mucor hiemalis f. hiemalis on the basis of various characteristics. The endo-beta-N-acetylglucosaminidase, named Endo-M, was purified to almost homogeneity by polyacrylamide gel electrophoresis involving ammonium sulfate fractionation, and column chromatographies on DEAE-Sepharose CL-6B, Sephadex G-200, hydroxylapatite, TSK-gel HW-65F and Con A-Sepharose 4B. The molecular weight of the enzyme was estimated to be about 95,000 by gel chromatography. The optimum pH was found to be 6.0-6.5 and the enzyme was stable in the pH range of 7 to 8. The enzyme showed high activity on dansyl ovalbumin glycopeptide, and also could act on dansyl transferrin glycopeptide, and dansyl asialotransferrin glycopeptide containing biantennary complex type sugar chains. The Km value for dansyl asialotransferrin glycopeptide as the substrate was 2.0 x 10(-3) M. The enzyme released complex type sugar chains from intact asialotransferrin without the addition of any detergent and the liberated sugar chains were identified by chromatography on a Bio-Gel P-4 column, calibrated with markers of known structure, and 1H-NMR analysis.

Acetylglucosaminidase↗
PubMed1990

[Successful treatment of CML in accelerated phase with mithramycin].

The patient, an 18-year-old male, was admitted on May 17, 1988, because of high-grade fever, neuralgia and generalized lymphadenopathy. Bone marrow examination revealed a large number of small nests with myeloid blastic cells negative for both peroxidase and TdT activity. Ph1 chromosome and bcr rearranged fragment were positive. On a diagnosis of CML in the accelerated phase, treatment was started with standard BHAC-DMP and vincristine. However, fever still persisted and hematological improvement could not be obtained. From September 20, 1988, mithramycin was given at 25 micrograms/kg every three days. No fever was noted and the NAP score decreased. However, fever reappeared despite the continuing treatment. Combination use of vincristine (1.0 mg/week) and mithramycin (25 micrograms/kg/week) was then begun, and the fever immediately disappeared. After mithramycin administration, a transient marked increase of neutrophils appeared in the peripheral blood, suggesting the induction of differentiation. After then, a complete remission was obtained. A transient disappearance of Ph1 chromosome by the chemotherapy was noticed. He has remained in the chronic phase of CML for one year. In conclusion, combination use of vincristine and mithramycin may be useful in the treatment of the myeloid blast crisis.

Adolescent↗
PubMed1989

Effect of aspirin on heparin-induced thrombocytopenia (HIT) in a patient requiring hemodialysis.

The present report describes the management of a 75-year-old uremic patient with delayed-onset heparin-induced thrombocytopenia and clot formation in extracorporeal circulation. The test for serum heparin-dependent platelet aggregation factor was positive and the serum platelet binding IgG (PBIgG) became elevated after the onset of heparin-induced thrombocytopenia. He required continuous exposure to heparin for hemodialysis. One gram of aspirin daily was begun to prevent clot formation in the circuit. Hemodialysis with full heparinization was achieved with no clot formation in the circuit. After aspirin ingestion, the increased level of patient's PBIgG in the presence of heparin and thrombocytopenia were restored to normal. Inhibition of platelet aggregation with aspirin allowed uneventful dialysis in a patient with heparin-induced thrombocytopenia.

Aged↗
PubMed1989

Mechanism for increase of gastrin release by secretin in Zollinger-Ellison syndrome.

In patients with Zollinger-Ellison syndrome, serum gastrin level is increased by secretin and is decreased by somatostatin. To elucidate the cellular mechanism for these actions, we investigated the direct effects of secretin and somatostatin on dispersed gastrinoma cells from a patient with Zollinger-Ellison syndrome. In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin. In the presence of guanosine 5'-triphosphate, furthermore, secretin enhanced adenylate cyclase activation in the membranes from these cells, and this activation was reduced by somatostatin, whereas neither secretin nor somatostatin affected inositol phospholipid turnover. On the other hand, removal of guanosine 5'-triphosphate from incubation medium abolished both the stimulatory effect of secretin and the inhibitory effect of somatostatin on adenylate cyclase activation. Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase. Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins.

Adenylyl Cyclases↗
PubMed1989

Prostaglandin E2 and F2 alpha inhibit growth of human gastric carcinoma cell line KATO III with simultaneous stimulation of cyclic AMP production.

The effects of prostaglandins (PGs) on the growth of human gastric carcinoma cell line KATO III were investigated. PGE2 as well as PGF2 alpha significantly and dose-dependently inhibited the growth of this gastric carcinoma cell line (PGE2 greater than PGF2 alpha). This inhibition of cell growth by the PGs was associated with the increase in cyclic AMP production (PGE2 greater than PGF2 alpha), whereas inositol-phospholipid turnover was not affected by either PGE2 or PGF2 alpha as assessed by the formation of 3H-inositol phosphates. Furthermore, the proliferation of these gastric carcinoma cells was also suppressed by the administration of forskolin as well as of dibutyryl cyclic AMP. These results suggest that PGE2 and PGF2 alpha inhibit the growth of cultured human gastric carcinoma cells KATO III via stimulation of cyclic AMP production.

Bucladesine↗
PubMed1989

Presence and release of calcitonin gene-related peptide in rat stomach.

Immunoreactive (IR)-calcitonin gene-related peptide (CGRP) was identified throughout the entire stomach of rats, being most highly concentrated in the pyloric region, and the concentrations in muscular layers being higher than those in mucosal layers. In addition, IR-CGRP was also present in the venous effluent from isolated perfused rat stomach, and its release was stimulated by dibutyryl cyclic AMP or theophylline but not by glucagon. Gel chromatography as well as HPLC of both tissue extracts and gastric perfusate showed three identical major peaks of IR-CGRP, one of which coeluted with synthetic CGRP. These results suggest that CGRP in the stomach plays a role in the regulation of gastric function.

Animals↗
PubMed1988

Effect of glucocorticoid administration on intestinal, renal, and cerebellar calbindin-D28K in chicks.

A radioimmunoassay for chick intestinal calcium-binding protein (calbindin-D28K, CaBP-28K) has been developed in our laboratory with a detection limit of 0.3 ng/ml. The values for CaBP-28K in vitamin D-deficient (-D) chicks ranged from a high value for the cerebellum (21,400 +/- 580 ng/mg protein) to a scarcely detectable level in the liver (19.6 +/- 2.2 ng/mg protein). After administration of vitamin D (vitamin D3 500 IU p.o. for 7 days) (+D), the levels of CaBP-28K increased in the duodenum (52,300 +/- 5,100 ng/mg protein), ileum (45,200 +/- 740 ng/mg protein), cerebellum (22,000 +/- 470 ng/mg protein), colon (15,200 +/- 330 ng/mg protein), and kidney (13,460 +/- 540 ng/mg protein). However, the increment in the level of CaBP-28K in each tissue after vitamin D administration was different; levels of CaBP-28K in the duodenum, ileum, and colon increased dramatically more than 200 times after vitamin D administration, whereas that in the kidney showed only a 2.5-fold increase and was unaltered in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Tolbutamide inhibits gastrin release in man.

Tolbutamide significantly decreased fasting plasma gastrin after 5 min of intravenous infusion in patients with atrophic gastritis, duodenal ulcer, or insulin-dependent diabetes mellitus (IDDM) as well as in healthy volunteers. Increased plasma insulin and decreased blood glucose were observed in patients with atrophic gastritis, duodenal ulcer and healthy volunteers, but not in patients with IDDM. Suppression of plasma gastrin in healthy volunteers was also observed following oral administration of tolbutamide. Despite the observed decrease in plasma gastrin, neither basal nor tetragastrin-stimulated acid output was changed for 30 min following tolbutamide infusion in healthy volunteers. Thus, our data suggest that tolbutamide inhibits gastrin release in man via mechanisms independent of changes in plasma insulin, blood glucose or acid secretion.

Adult↗
PubMed1988

A novel glycosphingolipid hydrolyzing enzyme, glycosphingolipid ceramide deacylase, which cleaves the linkage between the fatty acid and sphingosine base in glycosphingolipids.

It has been demonstrated that the GM2 ganglioside cannot be cleaved by exo-beta-N-acetylhexosaminidases isolated from molds or bacterial sources. Here, a novel GM2 ganglioside-degrading enzyme was found in cells of Nocardia sp. This enzyme releases free fatty acids from the GM2 ganglioside. The chemical structure of the resultant lyso-GM2 ganglioside has been characterized by fast atom bombardment mass spectrometry, gas chromatography, and proton nuclear magnetic resonance spectroscopy. Using 14C-labeled GM2, at the fatty acid moiety, with stearic acid as the substrate, the optimum pH was determined to be 5.8. The enzyme was demonstrated to be capable of releasing fatty acids from GM3, GM2, GM1, and GD1a, and from neutral glycosphingolipids including Gb3-Cer, asialo-GM2, and asialo-GM1, but not from sphingolipids including Cer, Gal-Cer, Glc-Cer, and Lac-Cer. This enzyme, tentatively called glycosphingolipid ceramide deacylase, was found to be a tightly membrane-bound enzyme.

Amidohydrolases↗
PubMed1988

Dual action of protein kinase C activation in the regulation of insulin release by muscarinic agonist from rat insulinoma cell line (RINr).

The role of protein kinase C in muscarinic agonist-induced insulin release from rat insulinoma cells was investigated. The dose-dependent stimulation of insulin secretion by carbamylcholine (carbachol) was associated with dose-dependent increase in the release of 3H-inositolphosphates from prelabeled rat insulinoma cell line (RINr) cells. After preincubation with 32P-orthophosphates, carbachol also evoked a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-bisphophate with concomitant increase in 32P-labeling of phosphatidic acid. Furthermore, carbachol significantly increased membrane-associated protein kinase C activity with a simultaneous decrease of its activity in cytosol. Although phorbol-12,13-dibutyrate (PDBu), a protein kinase C activator, also stimulated insulin release, insulin secretion induced by concomitant administration of carbachol and PDBu was clearly less than the level expected on the basis of an additive action. Moreover, PDBu significantly inhibited inositolphospholipid turnover stimulated by carbachol. Finally, PDBu inhibited the binding of 3H-scopolamine binding revealed that PDBu decreased the number of muscarinic receptors without altering its affinity. These findings suggest that activation of protein kinase C not only mediates muscarinic stimulation of insulin secretion from RINr cells but also operates a negative feedback mechanism in a signal transduction system, at least in part, via down-regulation of muscarinic receptors.

Adenoma, Islet Cell↗
PubMed1988

Calcitonin gene-related peptide stimulates adenylate cyclase activation via a guanine nucleotide-dependent process in rat liver plasma membranes.

To evaluate the functional relationship between the liver calcitonin gene-related peptide (CGRP) receptor and guanine nucleotide-binding proteins, we investigated the effects of nucleotides not only on adenylate cyclase activation by CGRP, but also on 125I-[Tyr0]rat CGRP binding to rat liver plasma membranes. In the presence of GTP, rat CGRP stimulated adenylate cyclase activity in a dose-dependent manner in rat liver plasma membranes, and this effect was reduced in the absence of GTP. Salmon calcitonin also enhanced adenylate cyclase activation in the presence of GTP, but only in higher concentrations. On the other hand, guanine nucleotides not only decreased 125I-[Tyr0]rat CGRP binding to rat liver plasma membranes, but also accelerated the dissociation of label binding, and the removal of Mg2+ from incubation medium attenuated this inhibitory action of GTP on 125I-[Tyr0]rat CGRP binding to membranes. Scatchard analysis of the data revealed that the reduction of 125I-[Tyr0]rat CGRP binding by GTP was due to the decrease in binding affinity without a significant change in binding capacity. These findings lead us to conclude that binding of CGRP to its receptors activates adenylate cyclase in rat liver plasma membranes via a guanine nucleotide-dependent process, suggesting the involvement of guanine nucleotide-binding stimulatory protein in the action of CGRP.

Adenylyl Cyclases↗
PubMed1987

Glucose stimulates insulin release without altering cyclic AMP production or inositolphospholipid turnover in freshly obtained human insulinoma cells.

Glucose, forskolin, IBMX and carbachol all stimulated insulin release from freshly obtained human insulinoma cells. In these same cells, cellular cyclic AMP levels were raised by forskolin and IBMX but not by glucose and carbachol. On the other hand, of all the insulin secretagogues examined, only carbachol stimulated the formation of 3H-inositol trisphosphate in these cells. Thus, in these insulinoma cells, glucose apparently induces insulin secretion without altering cyclic AMP production or inositolphospholipid turnover.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Effect of oral glucose administration on plasma growth hormone-releasing hormone (GHRH)-like immunoreactivity levels in normal subjects and patients with idiopathic GH deficiency: evidence that GHRH is released not only from the hypothalamus but also from extrahypothalamic tissue.

Using a specific and sensitive RIA for GH-releasing hormone (GHRH), we examined the effect of oral administration of 75 g glucose on peripheral plasma GHRH-like immunoreactivity (GHRH-LI) in normal subjects (n = 12) and patients with idiopathic GH deficiency (IGHD) (n = 6). The normal subjects had two peaks of plasma GHRH-LI after oral glucose administration. The initial peak GHRH-LI levels occurred 30-150 min after glucose ingestion and corresponded to an increase in blood glucose. The increment in plasma GHRH-LI levels 30 min after glucose ingestion [7.4 +/- 2.4 (+/- SEM) pg/ml] was significantly higher (P less than 0.05) than that during a control study. Second peaks in plasma GHRH-LI occurred 3.5-6 h after glucose ingestion, and the mean increment 5 h after glucose ingestion was 9.4 +/- 2.4 pg/ml. This second rise of plasma GHRH-LI coincided with a significant increase in plasma GH after reactive hypoglycemia. This second GHRH-LI peak and the rise of plasma GH after hypoglycemia were absent in patients with IGHD, whereas the first peak of plasma GHRH-LI appeared shortly after glucose ingestion in these patients as well as in normal subjects. In addition, hypoglycemia produced by iv injection of regular insulin (0.1 U/kg) was not accompanied by increases in plasma GHRH-LI and GH levels in patients with IGHD, whereas insulin-induced hypoglycemia resulted in significant elevations of both plasma GHRH-LI and GH levels in normal subjects. These findings suggest that peripheral plasma GHRH-LI is derived from the hypothalamus as well as from an extrahypothalamic source(s); extrahypothalamic GHRH is released shortly after glucose ingestion; and secretion of GHRH from the hypothalamus is stimulated by hypoglycemia.

Adolescent↗