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Biomedical subjects

H Manaka

Publications and source records attributed to H Manaka.

At least 55 records · Page 3Linked to original sources
PubMed1992

Role of Ca2+ on vasoactive intestinal peptide-induced glucose and adenosine 3',5'-monophosphate production in the isolated perfused rat liver.

Livers from fed rats (180-240 g) were perfused noncyclically with a hemoglobin-free medium in vitro to determine whether vasoactive intestinal peptide (VIP) increases hepatic glucose production through a cAMP- or a Ca(2+)-dependent mechanism. Glucose output did not increase, but cAMP increased maximally during 10(-9) M VIP infusion. When VIP was perfused at 10(-8) M or more, glucose output increased dose dependently, whereas cAMP increased only a little during the VIP infusion, but increased greatly after the infusion. When Ca2+ was excluded from the perfusate, glucose output produced by 10(-8)-10(-7) M VIP was only 40% of that observed in the Ca(2+)-containing perfusion, and the increase in cAMP was abolished almost completely. By adding 10(-7) M A23187 for 10 min during the infusion of 10(-9) M VIP, cAMP, which increased with VIP alone, decreased during the A23187 infusion and increased again after the cessation of the A23187 infusion, whereas glucose output increased during the A23187 infusion. These results were similar to those observed with higher concentrations of VIP. When 10(-4) M isobutylmethylxanthine and 10(-8) M VIP were infused concurrently, cAMP increased rapidly during the infusion and decreased after the infusion. In conclusion, 1) glycogenolysis is produced by VIP through a Ca(2+)-dependent mechanism, rather than a cAMP-dependent one; and 2) the restriction of cAMP accumulation during the infusion of high concentrations of VIP is caused by Ca(2+)-induced phosphodiesterase activation.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Calcitonin gene-related peptide immunoreactivity in familial amyotrophic lateral sclerosis.

The lumbar cords from 3 cases of familial amyotrophic lateral sclerosis (fALS), one case of vincristine neuropathy, and two control cases were examined with an antiserum to calcitonin gene-related peptide (CGRP). The anti-CGRP intensely labelled the spinal posterior horns in all cases. In the anterior horns, several perikarya and cord-like neuritic swellings, mostly axons, were labelled with the antibody in the fALS cases, whereas CGRP-positive structures were extremely rare in the cases other than fALS. It is possible that the accumulation of CGRP in the proximal axonal swellings and perikarya may result from entrapment of CGRP during the anterograde axonal transport, causing loss of, or decrease in, CGRP at the neuromuscular junction and producing weakness and atrophy of the muscles.

Adult↗
PubMed1991

Hyperglycaemia but not hyperinsulinaemia prevents the secretion of glucagon-like peptide-1 (7-36 amide) stimulated by fat ingestion.

The effect of insulin and glucose on fat-induced gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1 (7-36 amide)) was studied in five healthy subjects during continuous glucose infusion (Protocol 1) and during hyperinsulinaemic euglycaemic blood glucose clamp (Protocol 2). In Protocol 1, 50 g fat was orally ingested and glucose was infused at a rate of 0.7 g/kg/h for 2 h continuously from the time of fat ingestion. Either glucose infusion alone or fat ingestion alone was carried out in the same subjects as the control. The release of GIP and GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state. In protocol 2, 50 g of fat was ingested and insulin was infused at a rate of 0.1 U/kg/h with an artificial pancreas system to obtain the normoglycaemic hyperinsulinaemic state. The release of GIP was significantly suppressed in the normoglycaemic hyperinsulinaemic state as well as in the hyperglycaemic hyperinsulinaemic state. However, the release of GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state but not in the euglycaemic hyperinsulinaemic state. Thus, it is concluded that insulin inhibits fat-induced GIP, but not GLP-1 (7-36 amide), secretion and that glucose is likely to inhibit GLP-1 (7-36 amide) secretion.

Adult↗
PubMed1991

[A case of Creutzfeldt-Jakob disease with markedly elevated ubiquitin concentration in the cerebrospinal fluid].

A 56-year-old woman initially noticed dizziness in October, 1988, and later dementia and gait disturbance developed, associated with myoclonus and periodic synchronous discharge in the electroencephalogram. On the basis of these clinical findings we made a diagnosis of Creutzfeldt-Jakob disease (CJD). Using RIA for ubiquitin (signal peptide of the ATP dependent proteolytic system), we measured the cerebrospinal fluid (CSF) ubiquitin levels. The CSF level of ubiquitin was markedly elevated in this case five months after the initial symptoms (230.0 ng/ml) compared with normal values (14.3 +/- 1.1 ng/ml) and values in patients with senile dementia of Alzheimer type (21.3 +/- 6.1 ng/ml) and vascular dementia (16.6 +/- 6.4 ng/ml). With progression of brain atrophy in this case, CSF levels of ubiquitin rapidly decreased to near the normal values. These findings suggest that CSF ubiquitin concentration reflects the activity of the disease process in CJD, and it may be useful in the diagnosis of CJD.

Creutzfeldt-Jakob Syndrome↗
PubMed1989

Distribution and molecular forms of glucagon-like peptide in the dog.

Using glucagon-like peptide-1 N-terminus and C-terminus directed antisera, we investigated concentration and molecular forms of GLP-1 immunoreactivity (IR) in extracts of various tissues of the dog. GLP-1 IR measured with C-terminus-directed antiserum R2337 (GLP-1 IR-CT) was high in the ileum, appendix, jejunum, colon, and gastric fundus and body. GLP-1 IR measured with N-terminus-directed antiserum R1043 (GLP-1 IR-NT) was high only in the pancreas, and gastric fundus and body. Only GLP-1 IR-CT was found in the hypothalamus, thalamus and medulla oblongata. No immunoreactive materials were detected in the liver, spleen and kidney. Gel-filtration with Sephadex G-50 showed two peaks of both GLP-1 IR-CT and GLP-1 IR-NT, at 10kd and at the position of GLP-1 (1-36 amide) in the pancreatic extract, and one peak at 10kd in the stomach extract. Ileal extracts showed 3 peaks of GLP-1 IR-CT at 10kd, at the position of GLP-1(1-36 amide) and GLP-1(7-36 amide), respectively, but GLP-1 IR-NT was coeluted with GLP-1(1-36 amide). Hypothalamic extracts showed a single peak at the position of GLP-1(7-36 amide). These results suggest that processing of preproglucagon differs in different organs, and that the main GLP-1-related products are a large molecular form and GLP-1(1-36 amide) or GLP-1(1-37) in the pancreas, and GLP-1(7-36 amide) or GLP-1 (7-37) in the ileum and hypothalamus.

Animals↗
PubMed1989

Morphology of the canine pyloric sphincter in relation to function.

The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.

Animals↗
PubMed1989

Biochemical studies on opioid and alpha 2-adrenergic receptors in canine submucosal neurons.

Biochemical information about receptors for adrenergic and opioid neurotransmission in submucosal plexus (SMP) is unavailable. We have purified a fraction P2 enriched in synaptosomes and neuronal membranes (high [3H]saxitoxin binding and high vasoactive intestinal polypeptide immunoreactivity, low activity of 5'-nucleotidase) from the canine small intestine SMP. The synaptosomal fraction (fraction P2) also contained a high density of opioid diprenorphine binding sites of high affinity. [3H]rauwolscine binding was enriched both in fraction P2 and in a microsomal fraction. Competition experiments using several adrenergic and opioid receptor ligands revealed that opioid receptors were approximately 64% mu-, 24% delta-, and 12% kappa-subtypes and that adrenoceptors on fraction P2 were alpha 2-subtype but that there was a heterogeneous population of alpha 2-adrenoceptors. These studies show that a fraction enriched in synaptosomes and neural membranes from the canine intestine SMP contains opioid as well as alpha 2-adrenoceptors, that all three subtypes of opioid receptors seem to be present with mu-receptors predominant, and that subtypes of alpha 2-adrenoceptors appear to be present.

5'-Nucleotidase↗
PubMed1989

Release of VIP and substance P from isolated perfused canine ileum.

Basal release of vasoactive intestinal polypeptide (VIP) was 100-fold higher than substance P (SP) release from the vascularly perfused, neurally isolated canine small intestine. High-frequency field stimulation increased SP release but decreased VIP release. VIP release was markedly reduced by tetrodotoxin, perfusion with Ca-free medium, or by hexamethonium but not by atropine. Acetylcholine increased VIP output by an atropine-sensitive mechanism. Methionine-enkephalin or dynorphin (at 10-fold higher concentrations) markedly reduced VIP output; the actions of both these were abolished by naloxone. BHT-920, an alpha 2-adrenoceptor agonist, reduced VIP output markedly by a rauwolscine-sensitive mechanism. Isoproterenol and phenylephrine were without effect. Motilin produced persistent inhibition of VIP output. Thus VIP neurons of isolated canine small intestine were continuously active, driven by intrinsic cholinergic nerves, and subject to presynaptic inhibition by opioid agonists, alpha 2-adrenoceptor agonists, and motilin. This intrinsic neural system may provide tonic inhibitory control to the small intestinal circular muscle and provide a mechanism by which agents may modulate intestinal motor function.

Animals↗
PubMed1988

[3H]saxitoxin as a marker for canine deep muscular plexus neurons.

The objectives of this study are 1) to examine the potential of [3H]saxitoxin binding as a marker for the neuronal membranes in canine small intestinal muscle membrane preparations, 2) to develop a synaptosomal preparation from deep muscular plexus, and 3) to partially characterize [3H]saxitoxin binding to this fraction. A purified synaptosomal fraction, relatively low in the smooth muscle plasma membrane marker enzyme 5'-nucleotidase but enriched in [3H]saxitoxin binding (2,592 fmol/mg), was obtained on sucrose density gradient. Vasoactive intestinal peptide immunoreactivity was also highest (51.82 pmol/mg protein) in this fraction. The binding was rapid at 20 degrees C with quick and complete dissociation after the addition of excess unlabeled tetrodotoxin (TTX). Scatchard analysis of the saturation binding data revealed a single population of binding sites (Bmax = 5,705 fmol/mg protein). The affinity constants calculated from the kinetic and saturation data were in close agreement (Kd = 0.26 and 0.69 nM, respectively). TTX competed for the binding (Ki = 2.1 nM), whereas veratridine and guanidinium hydrochloride did not. Monovalent and divalent cations had differential effects on the binding.

Animals↗
PubMed1986

PHI structural requirements for potentiation of glucose-induced insulin release.

Immunoreactive PHI was detected in rat pancreas. The potentiating effect of 10(-9) M PHI upon insulin release from the isolated perfused rat pancreas was significant and most consistent when 250 mg% glucose was present in the perfusion medium. PHI(1-15) retained a substantial potentiating effect on insulin release, while PHI(14-27) was essentially inactive. Replacement of amino-terminal decapeptide portion of the PHI molecule with the corresponding part of VIP resulted in a drastic decrease of the potentiating effect of PHI on insulin release. 10(-8) M PHI(14-27) substantially diminished the potentiation by 10(-9) M PHI while PHI(1-15) was without an inhibitory effect. The present results indicate that the PHI active site for potentiation of glucose-induced insulin release resides in the amino-terminal segment of the molecule but requires the carboxyl terminal segment primarily for binding to exhibit full biological activity.

Animals↗
PubMed1984

125I-glucagon-degrading activity in acid-saline extracts of rat salivary gland.

The antibody-binding ability of the glucagon-like substance in rat submaxillary gland acid saline extract was examined by affinity chromatography, and the biological activity studied using the isolated liver perfusion method. We found that the glucagon-like substances in acid saline extract could not be bound to anti-glucagon antibody and that the gel-filtration peak on ultrogel AcA 54 could increase neither glucose nor cyclic AMP output from isolated perfused rat liver. Furthermore, the radioactivity peak of 125I-glucagon on Bio Gel P-6 column chromatography moved from its original position and eluted in later fractions after incubation with an acid saline extract of the submaxillary gland. In consequence, there was 125I-glucagon degrading activity in the submaxillary gland, but no glucagon-related peptide. Therefore, it is suggested that the glucagon-like substance, which has been reported in acid saline extract of the rat salivary gland, may be an artifact due to tracer degrading activity.

Animals↗
PubMed1984

Chromatographic differentiation of the mitochondrial and cytosolic fumarases of rat liver and Baker's yeast and differential induction of two fumarases of Baker's yeast.

The mitochondrial and cytosolic fumarases of rat liver could be separated from each other by Bio-Gel HTP column chromatography, showing that there are some conformational differences between the native proteins of the mitochondrial and cytosolic fumarases which have been indistinguishable by their physicochemical, catalytic, and immunochemical properties. The fumarase associated with the mitochondrial fraction of Baker's yeast could also be separated from that located in the cytosol by the Bio-Gel HTP column chromatography. By applying this chromatography to the differential determination of the fumarase activities in the Baker's yeast cultured under various conditions, it was shown that the mitochondrial and cytosolic fumarases in the cell are regulated by independent control systems.

Animals↗
PubMedDate not supplied

Stimulation of circular muscle motility of the isolated perfused canine ileum: relationship to VIP output.

Perfusion of ileal segments with tetrodotoxin; opioids, Met-enkephalin and dynorphin; and alpha 2 adrenoceptor agonist, BHT920, increased motility concomitant with the decreased VIP output into the venous effluent reported previously. This suggested that increased motility resulted from release of the muscle from tonic inhibition when VIP output was reduced sufficiently. However, blockade of nicotinic receptors also reduced VIP output but did not induce motility. Thus release of myogenic activity from inhibition is not a sufficient explanation for increased motility and a further excitatory mediator is required. Field stimulation of nerves increased VIP output and delayed distal contractions, suggesting that VIP does participate in the canine ileal distal inhibition reflex.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Mechanism of noncholinergic excitation of canine ileal circular muscle by motilin.

In the isolated perfused canine ileal segment, exogenous motilin infused for 9 min, at concentrations from 10(-10) M and 10(-8) M, increased circular muscle motility concomitant with inhibiting tonic VIP release, maximum at 10(-8) M. Both effects increased with increasing motilin concentrations. Atropine 10(-7) M pretreatment did not alter these responses. Naloxone 10(-7) M pretreatment eliminated both the increase in motor activity and the inhibition of VIP levels. Thus the nonmuscarinic neural pathway responsible for motor activation by motilin probably involves the stimulation of release of opiates, which in turn inhibit the release of VIP. Reduction of tonic inhibition of the muscle by continuous VIP release may in part account for increases in motor activity induced by motilin.

Animals↗
PubMedDate not supplied

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in a rural area of Japan. The Funagata diabetes study.

PURPOSE: To determine the prevalence of type 2 diabetes and impaired sucrose tolerance (IGT) among people aged 40 and over in a rural area, Funagata, Japan, by using a 75-g oral glucose tolerance test (OGTT), and to compare the prevalence to that obtained from a more urban area, Hisayama, Japan. METHODS AND RESULTS: Total eligible subjects for the Funagata study were 3526. Among them, 140 were confirmed to have diabetes judged by the 1985 WHO criteria. A 75-g OGTT was conducted, excluding the 140 known cases of diabetes. The 1985 WHO criteria were used to classify the current diabetes status of participants. The overall participation rate was 74.4%. The prevalence of diabetes (known and newly diagnosed cases combined) was 9.1% for men and 10.8% for women. The prevalence of IGT was 12. 0% for men and 16.5% for women. Age-adjusted prevalence (using 1990 Japanese census) of diabetes and IGT in men in Hisayama is two times higher than in Funagata (12.8% vs. 6.8% for diabetes, 19.5% vs. 10. 3% for IGT). Age-adjusted prevalence of IGT in women in Hisayama is significantly higher than in Funagata. CONCLUSIONS: The prevalence of type 2 diabetes among people aged 40 and over is approximately 10% even in a rural area of Japan. Prevalence of diabetes and IGT is much higher in an urban area than in a rural area in Japan.

Adult↗
PubMedDate not supplied

Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients.

Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP-1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP-1 were estimated by the difference between the values measured with the N-terminal directed antiserum (GLP-1NT) and those with the C-terminal directed antiserum (GLP-1 CT). Plasma levels of GLP-1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP-1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP-1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP-1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP-1 response appears to be characteristic of obese Type 2 diabetes.

Adult↗