Search PubMed⌕ Search

Biomedical subjects

K Tatemoto

Publications and source records attributed to K Tatemoto.

At least 19 recordsLinked to original sources

Gene expression profile in rat pancreatic islet and RINm5F cells.

To clarify tissue-specificity of pancreatic beta cells, comparison of mRNA expression in various conditions of the tissue of multiple organisms is important. Although the developed methodologies for mRNA monitoring such as microarray, rely on the growth of dbEST (database of expressed sequence tag), a large number of unknown genes in the genome, especially in the rat, have not been shown to be expressed. In this study, we have established the first database of ESTs from rat pancreatic islet and RINm5F cells. Two cDNA libraries were constructed using mRNAs from rat pancreatic islet and RINm5F cells to cover a wider spectrum of expressed genes. Over 40,000 clones were randomly selected from the two libraries and partially sequenced. The sequences obtained were subjected to BLAST database analyses. This large-scale sequencing generated 40,710 3'-ESTs. Clustering analysis and homology search of nucleotide and peptide databases using both 3'- and 5'-ESTs revealed 10,406 non-redundant transcripts representing 4078 known genes or homologs and 6328 unknown genes. To confirm actual expression, the unknown sequences were further subjected to dbEST search, resulting in the identification of 5432 significant matches to those from other sources. Interestingly, of the remaining sequences showing no match, 779 were found to be encoded by exon-intron organization in the corresponding genomic sequences, suggesting that these are newly found as actually expressed in this study. Since many genes are up- or down-regulated in differing conditions, applications of the expression profile should facilitate identification of the genes involved in cell-specific functions in normal and disease states.

Animals↗

The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.

Apelin is an endogenous ligand of the human orphan receptor APJ. We detected apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer cells in the liver. We also detected apelin-like immunoreactivity localized within the endothelia of small arteries in various organs. Further, it was found that mean arterial pressure after the administration of apelin-12, apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26+/-5, 11+/-4, and 5+/-4 mm Hg, respectively. In the presence of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on blood pressure was abolished. Furthermore, the administration of apelin-12 (10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate concentration from a basal level of 21.4+/-1.6 to 27.0+/-1.5 microM. Thus, apelin may lower blood pressure via a nitric oxide-dependent mechanism.

Animals↗

Apelin peptides block the entry of human immunodeficiency virus (HIV).

The orphan G protein-coupled receptor APJ has been shown to be a coreceptor for human and simian immunodeficiency virus (HIV and SIV) strains. We have determined that some HIV and SIV strains use APJ as a coreceptor to infect the brain-derived NP-2/CD4 cells. Because apelin is an endogenous ligand for the APJ receptor, we examined the inhibitory effects of apelin peptides on HIV infection, and found that the apelin peptides inhibit the entry of some HIV-1 and HIV-2 into the NP-2/CD4 cells expressing APJ. The inhibitory efficiency has been found to be in the order of apelin-36>apelin-17>apelin-13>apelin-12.

Amino Acid Sequence↗

[Automated infant auditory screening using the Natus-ALGO 2e in the NICU].

Natus-ALGO 2e, an automated ABR screener(Natus Medical, Foster City, CA, USA), compares the V wave of ABR evoked by 35-dB-nHL click stimuli by using a template-matching detection algorithm that provides only a pass-refer outcome. The aim of this study was to compare Natus-ALGO 2e with conventional ABR, and to evaluate its usefulness. The Natus-ALGO 2e screener was used to screen 202 ears of 101 neonates in our neonatal intensive care unit. The mean conceptional age at the time of screening was 40.4 +/- 3.0 weeks. 60 ears of 30 infants at high-risk of hearing impairment, including "refer" infants, were tested by the Natus-ALGO 2e and conventional ABR methods, and the results were compared. All neonates were tested with the Natus-ALGO 2e screener in a state of natural sleep, and screening time averaged 2 minutes 58 seconds. There were 97 cases in which both ears were passed, 3 cases in which both ears were referred, and one case in which one ear was referred. In comparison with conventional ABR, 53 of the 60 ears of 30 high-risk infants passed by the Natus-ALGO 2e method, whereas 14 of the 53 ears initially failed the conventional ABR screening. Of these 14 ears disagreements (the results of the Natus-ALGO 2e method passed, but the results of the conventional ABR failed), the results of the ABR screening changed to normal in 11 ears, and ABR showed improved threshold and latency in the other 3 ears after 5 weeks to 12 months. Among those that passed the Natus-ALGO 2e screening, the number of sweeps that failed the ABR screen was significantly greater than with normal ABR. Of the 7 ears of 4 patients that were referred on the basis of the Natus-ALGO 2e screening and failed by the conventional ABR method, 3 ears screened by the ABR method were normal when retested, and one ear passed by the Natus-ALGO 2e screening 12 weeks to 11 months later. In conclusion, Natus-ALGO 2e is useful for screening infant hearing because it can be performed quickly while the patient is sleeping naturally. In infants at high-risk for hearing impairment, the results of Natus-ALGO 2e and conventional ABR screening conflicted in numerous sweeps. Therefore, when there are many sweeps in high-risk infants, a retest should be performed that includes conventional ABR, even if they passed with Natus-ALGO 2e.

Audiometry, Evoked Response↗

[Search for an endogenous ligand of the orphan G protein-coupled receptor--discovery of apelin, a novel biologically active peptide].

In the search for an endogenous ligand of the human orphan receptor APJ, we have isolated from bovine stomach extracts a novel 36-amino acid peptide, designated apelin. The APJ receptor is one of the G protein-coupled orphan receptors, many of which have been considered to be specific receptors for unidentified hormones and neuropeptides. We recently found the presence of apelin in the adipocytes and vascular walls as well as in the stomach. We examined biological activities of apelin and found that apelin lowered blood pressure in rats and also released cholecystokinin(CCK) from dispersed intestinal endocrine cells. Since apelin is an endogenous ligand for the HIV entry coreceptor APJ, we tested the effect of apelin on the entry of HIV in association with CD4, and found that apelin blocked the entry of HIV-1 and HIV-2.

Amino Acid Sequence↗

Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum.

By using a strategy that we have developed to search for the ligands of orphan seven-transmembrane-domain receptors [S. Hinuma et al., Nature 393 (1998) 272-276], we have recently identified a natural ligand, apelin, for the orphan 7TMR, APJ [K. Tatemoto et al., Biochem. Biophys. Res. Commun. 251 (1998) 471-476]. In this paper, we isolated rat and mouse apelin cDNAs, and analyzed the tissue distribution of apelin mRNA in rats. Although apelin mRNA was widely detected in a variety of tissues, the highest expression of apelin mRNA was detected in the mammary gland of pregnant rats. In the mammary gland, biologically active apelin and its mRNA considerably increased during pregnancy and lactation, and reached a maximal level around parturition. Moreover, a large amount of apelin (14-93 pmol/ml) was found to be secreted in the bovine colostrum, and it was still detectable even in commercial bovine milk. Since apelin partially suppressed cytokine production by mouse spleen cells in response to T cell receptor/CD3 cross-linking, the oral intake of apelin in the colostrum and milk might modulate immune responses in neonates.

Adipokines↗

Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries.

Uric acid values in serum have been analyzed as one of the markers to predict cellular damage due to ischemia reperfusion injury in the field of organ transplantation. The present study was conducted to confirm that uric acid values in serum could be an efficient marker of ischemic injury of liver parenchyma following hepatic vascular occlusion in human liver surgery. The changes in serum uric acid values were analyzed at fixed intervals during different liver surgeries. Significant increases in serum uric acid values were observed in patients who received the Pringle's maneuver in which hepatic vascular inflow was manipulated with a repetition of 15 min occlusion and 5 min perfusion, whereas almost no changes in uric acid values were found in both groups of patients who received the hemilobal occlusion of the Glisson's triad in which the right or left vessels were manipulated with a repetition of 30 min occlusion and 5 min perfusion and the "control method" in which the hepatic vessels of the lesion side were previously cut before liver resection. Uric acid values in serum increased in patients of Pringle's maneuver compared to those of the hemilobal occlusion of the Glisson's triad and the control method though these procedures were used in larger hepatectomies rather than Pringle's maneuver. The results indicated that serum uric acid values do not always reflect the severity of ischemia of the liver parenchyma but reflect intestinal congestion because marked intestinal congestion was observed in patients of Pringle's maneuver but not in patients of the hemilobal occlusion of the Glisson's triad and the control method. The evaluation of the severity of the ischemic injury of the liver should be done with caution when uric acid is used as a marker in human liver surgery.

Adolescent↗

Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.

In the search for an endogenous ligand of the orphan G protein-coupled receptor APJ, the presence of the ligand in various tissue extracts was examined by measuring the increase in extracellular acidification rate of the cells expressing the APJ receptor as a specific signal induced by the interaction of the receptor and ligand. By monitoring this activity, we isolated an APJ receptor ligand, designated apelin, from bovine stomach extracts. The structures of bovine and human apelin preproproteins were deduced from the sequences of the corresponding cDNAs. The preproproteins consisted of 77 amino acid residues, and the apelin sequence was encoded in the C-terminal regions. Synthetic peptides derived from the C-terminal amino acid sequence of bovine preproapelin were capable of specifically promoting the acidification rate in the cells expressing the APJ receptor in a range from 10(-7) to 10(-10) M, indicating that apelin is an endogenous ligand for the APJ receptor.

Amino Acid Sequence↗

Regulation of the action of the novel cholecystokinin-releasing peptide diazepam binding inhibitor by inhibitory hormones and taurocholate.

Diazepam binding inhibitor (DBI1-86) has recently been isolated in search for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic secretion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and in vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secretion. Somatostatin, peptide YY (PYY) and taurocholate are known to inhibit feedback-stimulated CCK release in the rat. In this study, we investigated the effect of somatostatin, PYY and taurocholate on DBI-stimulated CCK secretion. Dispersed rat intestinal mucosal cells were prepared from the proximal small bowel and continuously perfused. The perfusate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effect at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pretreatment of the cells with pertussis toxin fully reversed the inhibitory effect of somatostatin on DBI-stimulated CCK secretion, suggesting that somatostatin exerts its action by an inhibitory G-protein. In contrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mechanisms to inhibit feedback-stimulated CCK release.

Animals↗

A culture substratum appropriate for brain cells is a chondroitin sulfate glycosaminoglycan in serum.

When cells dissociated from the neonatal rat brains are plated on a poly-lysine-coated surface in a serum-free medium, they display a strange morphology: a dark and extended cell body. Preincubation of the surface with fetal bovine serum was found to inhibit the appearance of this strange contraction of the basal cell sheets in a dose-dependent manner. This finding indicated the presence of a factor(s) in the serum, which might be an appropriate substratum for prolonged survival of brain neurons. In the current study, this factor was highly purified through DEAE ion-exchange chromatography followed by gel filtration. The factor was eluted from a Superose column at fractions corresponding to a molecular weight greater than 1000 kDa. By SDS-PAGE analysis, these fractions were found to contain a major band (>/=1000 kDa) positive for alcian blue and few minor bands faintly stainable with Coomassie blue. The activity of the purified sample, inducing the morphological change in cells, was diminished by incubation with chondroitinase ABC. Neither heparitinase II, hyaluronidase, nor trypsin modified the activity. An authentic chondroitin sulfate (type B) mimicked the serum action on the morphology of brain cells in early stages of culture. Taking these findings together, it is suggested that the factor in serum beneficial for the attachment of brain cells is composed of a chondroitin sulfate with a Mr greater than 1000 kDa. Cortical cells dissociated from the neonatal rat brain attached well to the purified factor-coated surface and displayed a healthy morphology: an optically-reflective cell body with thick neurites for at least 3 days in the absence of serum.

Animals↗

Hyperpolarization-activated Cl- current elicited by pituitary adenylate cyclase activating polypeptide in Xenopus oocytes.

We examined the electrophysiological effect of pituitary adenylate cyclase activating polypeptide (PACAP) in isolated Xenopus laevis oocytes in vitro. In conventional two-electrode voltage clamp experiments, PACAP (1-10 microM) activated an inward rectifier current at membrane potentials more negative than -60 mV without causing any significant change in currents at potentials more positive than -60 mV both in the follicle-enclosed oocyte and in the defolliculated oocyte. This current reversed at -22.5 mV, close to the theoretical value of Cl- equilibrium potential and the reversal potential of this current was shifted positively by reducing [Cl-]o. This current was blocked by Cl- channel blocker SITS and Ba2+. Furthermore, VIP and adenylate cyclase activator forskolin did not elicit the currents. In conclusion, PACAP elicited the hyperpolarization-activated Cl- current in Xenopus laevis oocytes. This current may modulate the membrane potential of the oocyte, thereby affecting the oocyte physiology.

Animals↗

Uric acid changes in serum during different forms of hepatic vascular inflow occlusion.

The present study was conducted to develop an efficient marker which can evaluate the influence of the occlusion of hepatic vascular inflow, which technique is commonly used in major liver surgery or in liver transplantation. Serum samples from the rats induced by hepatic vascular inflow occlusion were analyzed with high performance liquid chromatography with the electrochemical detection, and a substance which changed in accordance with the duration of the occlusion was obtained. Both the retention time and the ultraviolet absorption spectra of the substance completely agreed with those of an authentic uric acid and the substance was ultimately determined to be uric acid. To evaluate the changes in serum uric acid during different forms of hepatic vascular inflow occlusion we devised the four types of experimental model, viz. the occlusion of hepatic artery, portal vein, both hepatic artery and portal vein and both hepatic artery and portal vein of left hepatic lobes. From the device of experiments our results indicated that in the early stage of hepatic vascular inflow occlusion the high values of serum uric acid did not reflect the damage of hepatic circulation but rather responded to the intestinal congestion. Our results also indicated that even after the declamping of hepatic vascular inflow if high values of serum uric acid are prolonged it means the deterioration of the portocaval circulation including both intestinal and hepatic circulation. So that the evaluation of the severity of injured liver due to hepatic vascular inflow occlusion should be done with the caution especially in vivo study when uric acid values are used as a marker.

Animals↗

Islet hormone secretion in pancreatic cancer patients with diabetes.

The diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.

Adenocarcinoma↗

Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine.

Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK) and thus exert feedback control of pancreatic exocrine secretion. Exclusion of proteases from the duodenum either by the diversion of bile-pancreatic juice or by the addition of protease inhibitors stimulates exocrine pancreatic secretion. The mechanism by which pancreatic proteases in the duodenum regulate CCK secretion is unknown. In this study, we isolated a trypsin-sensitive peptide that is secreted intraduodenally, releases CCK, and stimulates pancreatic enzyme secretion in rats. This peptide was found to be identical to the porcine diazepam binding inhibitor by peptide sequencing and mass spectrometry analysis. Intraduodenal infusion of 200 ng of synthetic porcine diazepam binding inhibitor1-86 in rats significantly stimulated pancreatic amylase output. Infusion of the CCK antagonist MK-329 completely blocked the diazepam binding inhibitor-stimulated amylase secretion. Similarly, diazepam binding inhibitor33-52 [corrected] also stimulated CCK release and pancreatic secretion in a dose-dependent manner although it was 100 times less potent than the whole peptide. Using a perfusion system containing isolated mucosal cells from the proximal intestine of rats, porcine diazepam binding inhibitor 10(-12) M) dose dependently stimulated CCK secretion. In separate studies, it was demonstrated that luminal secretion of the diazepam binding inhibitor immunoreactivity (7.5 X 10(11) M) could be detected in rat's intestinal washing following the diversion of bile-pancreatic juice. The secretion of this peptide was inhibited by atropine. In conclusion, we have isolated and characterized a CCK-releasing peptide that has a sequence identical to the porcine diazepam binding inhibitor from pig intestinal mucosa and that stimulates CCK release when administered intraduodenally in rat. This peptide may mediate feedback regulation of pancreatic enzyme secretion.

Amino Acid Sequence↗

Activation of iron handling system within the gerbil hippocampus after cerebral ischemia.

Analyzing the distribution pattern of transferrin (Tf) and ferritin, we investigated the changes in iron metabolism related proteins in the process of neuronal death induced by 5 min ischemia. In the control animals, Tf immunoreactivity was localized in the oligodendrocytes. Ferritin was distributed in both neurons and gliacytes, particularly microglia. In parallel with the delayed neuronal death, Tf-positive atrophied neurons and numerous ferritin-positive gliacytes appeared in the CA1 subfield of the hippocampus 4 days after ischemia, when glia fibrillary acidic protein (GFAP)-positive astrocytes also appeared throughout the hippocampal structure. A considerable number of ferritin-positive phagocytes (reactive microglia) appeared in the stratum pyramidale from the seventh day. Our data show clearly that the mobilization of Tf and ferritin-positive phagocytes are linked with the degeneration of neurons induced by cerebral ischemia. These events may suggest an activation of iron handling system under the postischemic condition.

Animals↗

Bradykinin increases intracellular free Ca2+ concentration and promotes insulin secretion in the clonal beta-cell line, HIT-T15.

We have examined the effects of bradykinin (BK) on both the intracellular free calcium concentration ([Ca2+]i) and insulin secretion in the hamster beta-cell line, HIT-T15 cells. BK evoked a rise in [Ca2+]i in a dose-dependent manner. This response was suppressed by neomycin, suggesting that BK mobilizes Ca2+ from intracellular store via promotion of the phosphatidyl inositol turnover. Furthermore, BK also evoked insulin secretion. Both the BK-evoked rise in [Ca2+]i and insulin secretion were suppressed by the BK2 receptor antagonist, but not by the BK1 receptor antagonist. These results indicate that BK increases [Ca2+]i via BK2 receptor, thereby promoting insulin secretion in HIT-T15 cells.

Animals↗

GLP-1 depolarizes the rat pancreatic beta cell in a Na(+)-dependent manner.

An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent candidate for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell. Endocrinol., 96 (1993) 85-90) that GLP-1 increased both insulin secretion and the efflux of 45Ca2+ in a Na(+)-dependent manner. Further, GLP-1 depolarizes the pancreatic beta cells in the presence of high concentration of glucose. Here, we report the effect of GLP-1 on the membrane potential with a physiological concentration of glucose in perforated patch clamp of primary cultured rat beta cells. 10 nM GLP-1 depolarized the beta cell, which was completely reversed by replacing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+ channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpolarizing the cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by a prior replacement of Na+ with NMDG. In addition, GLP-1 slightly augmented the long-lasting Ba2+ current, which was reverted to the control level by a selective inhibitor of protein kinase A, H-89. These results indicate: (i) GLP-1 depolarizes the beta cell by activating the membrane Na+ permeability; (ii) GLP-1 slightly modulates the L-type Ca2+ channel probably through protein kinase A; and (iii) at least in part, these mechanisms may be involved in the insulin secretion induced by GLP-1.

Animals↗

Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells.

Pancreastatin (PST) is known to inhibit glucose-stimulated insulin release both in vivo and in vitro, but it has not been determined whether PST acts directly on pancreatic B-cells and no study has been reported on the effect of PST on the intracellular free Ca2+ concentration ([Ca2+]i) in pancreatic islet cells. In the present study, by using the dissociated rat pancreatic B-cells, we examined the effects of PST on the increase in [Ca2+]i induced by several insulin secretagogues, and compared them with those of somatostatin (SRIF). PST (1-100 nM) dose-dependently inhibited the glucose-induced rise in [Ca2+]i in single pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-induced rise in [Ca2+]i. These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 microM) with 5.5 mM glucose induced a biphasic increase in [Ca2+]i in single islet cells. SRIF (10 nM) suppressed the second phase in [Ca2+]i increase without affecting the first phase. In contrast, PST (100 nM) had no effect on the ACh-induced response. Gastric inhibitory polypeptide (100 nM) with 5.5 mM glucose induced a rise in [Ca2+]i in single islet cells. SRIF inhibited this increase, but PST did not. Both PST and SRIF failed to affect the sustained rise in [Ca2+]i evoked by excess K+. These results suggest that PST and SRIF suppress the glucose-induced insulin secretion at least partly by inhibiting the rise in [Ca2+]i in pancreatic B-cells. Furthermore, PST may suppress the glucose-induced rise in [Ca2+]i via a mechanism different from that of SRIF.

Acetylcholine↗