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Biomedical subjects

M Ui

Publications and source records attributed to M Ui.

At least 289 records · Page 16Linked to original sources
PubMed1982

Glycogen storage myopathy with abnormal lactate dehydrogenase.

We studied a 3 year old girl with mental retardation and limb muscle weakness. The muscle glycogen content was 17.4 mg/g tissue, which was approximately three times higher than normal. There were no other known abnormalities noted in this child that could explain the cause of glycogen storage disease. Our in vitro glycolysis study showed marked increase of pyruvate, but no increase in lactate levels. The observed results suggested to us that an abnormal lactate dehydrogenase might account for the abnormal accumulation of glycogen in the muscle.

Child, Preschool↗
PubMed1982

Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein.

GTP and isoproterenol activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in washed membranes prepared from C6 gliomas cells was enhanced by incubation with islet-activating protein, one of the pertussis toxins, if the incubation mixture was supplemented with NAD and ATP. The action of the protein was observed immediately after its addition and increased progressively in magnitude as the protein concentration or the incubation time increased. There was simultaneous incorporation of radioactivity from the ADP-ribose moiety of variously labeled NAD into the membrane protein with a molecular weight of 41,000. We conclude that islet-activating protein enhances receptor-mediated GTP-induced activation of membrane adenylate cyclase as a result of ADP-ribosylation of a membrane protein, probably one of the components of the receptor-adenylate cyclase system.

Adenosine Diphosphate Ribose↗
PubMed1982

Plasma guanosine 3',5'-monophosphate responses to methacholine and epinephrine in humans.

The im injection of methacholine into healthy volunteers caused a dose-dependent increase in plasma cGMP levels; this increase was antagonized by atropine, while it was not affected by phentolamine or propranolol. The im injection of epinephrine caused a small but significant rise in plasma cGMP concentrations; this rise was completely blocked by the simultaneous injection of phentolamine, while it was not affected by atropine or propranolol. These data show that changes in the plasma concentration of cGMP may reflect not only cholinergic but also alpha-adrenergic functions in humans.

Adolescent↗
PubMed1982

Alpha 2-adrenergic inhibition of insulin secretion via interference with cyclic AMP generation in rat pancreatic islets.

Glucose-induced secretion and cyclic AMP accumulation in isolated rat pancreatic islets as well as GTP-activated adenylate cyclase of the membrane-rich preparation from the islets were strongly inhibited by some alpha-adrenergic agonists. The relative potencies of the agonists, estimated according to their dose-dependent actions, were in such an order that clonidine greater than epinephrine (congruent to norepinephrine) greater than phenylephrine congruent to methoxamine, regardless of which of the three parameters (i.e., insulin release, cyclic AMP accumulation, and adenylate cyclase activity) was used for estimation. There was a highly significant correlation between the amounts of cyclic AMP accumulation and the rate of insulin release that were changed in response to these agonists. The order of the potencies of alpha-adrenergic antagonists to reverse epinephrine inhibition of these parameters was invariably yohimbine congruent to dihydroergotamine congruent to phenylephrine greater than prazosin. In conclusion, the rat islet cell membrane is equipped with alpha 2-adrenoceptors which are linked to adenylate cyclase to cause diminution of the cellular content of cyclic AMP; insulin secretion may be inhibited consequently.

Adenylyl Cyclases↗
PubMed1981

Islet-activating protein. A modifier of receptor-mediated regulation of rat islet adenylate cyclase.

Adenylate cyclase of the membrane-rich fraction of 24-h cultured islets was inhibited by epinephrine via alpha-adrenergic receptors. Epinephrine was inhibitory only when the enzyme was activated by GTP; the degree of inhibition was highly proportional to the degree of GTP activation. Adenylate cyclase of islets cultured with islet-activating protein (IAP), one of the pertussis toxins, was less susceptible to epinephrine inhibition. The degree of the inhibition was markedly reduced without changes in potency of the catecholamine and in GTP dependence after IAP treatment. None of the other kinetic properties of the enzyme including the affinity for substrate, sensitivity to guanine nucleotide and fluoride activation, and cholera toxin-induced modification of enzymic activity were affected by treatment of islets with IAP, suggesting that neither the catalytic nor the GTP-regulatory component of the membrane adenylate cyclase complex is the site of IAP action. Slight activation of the enzyme by glucagon or adenosine tended to be enhanced by IAP treatment. Thus, a mechanism whereby membrane receptors are linked to adenylate cyclase appears to be modified by exposure of islet cells to IAP.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1981

Modification by islet-activating protein of receptor-mediated regulation of cyclic AMP accumulation in isolated rat heart cells.

Free cells isolated from adult rat heart by the collagenase method were maintained in culture up to 21 h with or without an islet-activating protein (IAP) that had been purified from the culture medium of Bordetella pertussis. Short-term stimulation of beta-adrenergic or glucagon receptors in these cultured cells caused more accumulation of cAMP in cells precultured with IAP (IAP-treated) than in nontreated cells, although there was no significant difference in the baseline (non-stimulated) content of cAMP between these cells. Stimulation of muscarinic cholinergic or adenosine R-site receptors caused a marked inhibition of cAMP accumulation in nontreated cells in either the presence or absence of a beta-agonist (or glucagon); no such inhibition was essentially observed in IAP-treated cells. These actions of IAP developed gradually and were dose-dependent with the half-maximal concentration of approximately 80 ng/ml in culture. It is concluded that IAP may exert its unique influence on the heart cell membrane causing profound modification of the coupling mechanism involved in the receptor-mediated activation or inhibition of adenylate cyclase. This action of IAP differs clearly from that of cholera toxin which activates adenylate cyclase rather independently of the receptor functions in heart cells.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Adrenergic mechanisms in the hyperglycaemia and hyperinsulinaemia of diabetic KK mice.

Simultaneous occurrence of hyperglycaemia (up to 300 mg/100 ml) and hyperinsulinaemia (up to 1200 mu U/ml) was evident in the fed state in genetically diabetic KK mice, indicating insulin resistance. The hyperinsulinaemia was enhanced by alpha-adrenergic blockade and alleviated by B-blockade. Epinephrine-induced hyperglycaemia and isoproterenol-induced hyperinsulinaemia, both of which could be blocked by beta-adrenergic antagonists, were more marked in KK mice than in ICR mice. A possible significance of adrenergic mechanisms is discussed with respect to the aetiology of the metabolic disturbances characteristic of KK mice.

Animals↗
PubMed1981

Turnover rate of blood glucose in diabetic KK mice.

Metabolic rate constants for blood glucose turnover were estimated based on the decay of [U-14C, 6-3H]glucose injected intravenously in genetically diabetic KK mice. Comparison was made with the rate constants similarly obtained with non-diabetic and streptozotocin-induced diabetic ICR mice. Recycling of blood glucose via the Cori cycle, as estimated from the difference in the decay rate between 14C and 3H, was more active in KK mice than in non-diabetic and diabetic ICR mice. The Cori cycle activity was reduced by beta-adrenergic blockade in KK mice and was enhanced by alpha-blockade in ICR mice. It is concluded that predominance of beta-adrenergic functions in KK mice is responsible for activation of the Cori cycle as one of the mechanisms for metabolic resistance to endogenous insulin.

Animals↗
PubMed1981

Role of chemosensitivity during exercise in normal subjects and patients with pulmonary emphysema.

In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients.

Adult↗
PubMed1981

Plasma cyclic AMP hyper-response to glucagon in manic patients on lithium treatment.

We have measured the rise in plasma cyclic AMP induced by glucagon and adrenaline in manic patients on lithium therapy. Glucagon-induced increases in the concentration of plasma cyclic AMP were larger, but the adrenaline-induced increases were smaller, in lithium-treated manic patients than in normal controls. In 3 manic patients, the enhanced response to glucagon was normalized 3 weeks after the cessation of lithium treatment. Though the underlying mechanism is unknown, the unusual plasma cyclic AMP responses may reflect altered receptor sensitivity which would be closely related to the curative effect of lithium on symptoms of mania.

Adult↗
PubMed1981

In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux.

Pancreatic islets were maintained in culture with or without islet-activating protein (IAP), which is a new protein purified from culture medium of Bordetella pertussis. These cultured islets (IAP-treated or control) were then incubated for 30 min in IAP-free medium with various insulin secretagogues. During incubation, much more insulin was released from IAP-treated islets than control islets in response to glucose, arginine, glucagon, and sulfonylurea. IAP was effective in this regard when added to cultures at concentrations higher than 0.01 ng/ml; the effect was dependent on concentration up to 100 ng/ml. Enhanced insulin secretion was associated with accumulation of cyclic AMP when breakdown of the nucleotide was prevented by a methylxanthine. Epinephrine caused marked inhibitions, via alpha-adrenergic receptors, of glucose-induced insulin release, cyclic AMP accumulation and 45Ca uptake in control islets but did not in IAP-treated islets during incubation. None of these effects of IAP pretreatment were observed unless the medium for incubation was supplemented with Ca ions. 45Ca ion flux through the islet cell membrane was accelerated by the IAP treatment; conceivably, IAP was effective in causing sustained activation of native calcium ionophores on the membrane, which would be responsible for the enhanced insulin and cyclic AMP responses characteristic of IAP-treated islets.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Slow interaction of islet-activating protein with pancreatic islets during primary culture to cause reversal of alpha-adrenergic inhibition of insulin secretion.

The manner in which islet-activating protein (IAP), a protein purified from the culture medium of Bordetella pertussis, interacts with the islet B-cell was studied by following the progressive development of IAP-induced reversal of alpha-adrenergic inhibition of insulin release during maintenance of islets in culture with glucose and epinephrine. This action of IAP developed in an exponential manner dependent on its concentration after a true lag period of about 1 h. The lag period was not grossly dependent on the concentration of IAP added but highly dependent on temperature of culture, and was still seen upon adding a second dose of IAP to partially stimulated cells. After 24-h culture significantly more insulin was secreted with IAP at a concentration as low as 1 pg/ml and the half-maximal effect was observed at 0.1 ng/ml. The development of IAP action occurred even in the islets that had been exposed to IAP for only 30 s, but was significantly prevented by anti-IAP serum added before the end of the lag period. IAP was effective in the presence of cycloheximide, an inhibitor of protein synthesis, or of vinblastine or cytochalasin B, microtubular-microfilamentous modifiers. It is suggested that the IAP molecule is rapidly bound to the receptor area of the islet B-cell and then is gradually inserted into the cell membrane before appearance of its action to activate native calcium ionophores. This slow interaction of IAP with the membrane may be responsible for potentiation of insulin secretory and cAMP responses of the cell to various stimuli as well as for reversal of alpha-adrenergic inhibition.

Animals↗
PubMed1980

Glycogen metabolism in rat liver during transition from the fed to fasted states.

Hepatic glycogen metabolism was studied in rats during the period of transition from the fed to fasted states. Glycogenic activity was measured in vivo based on the incorporation of [14C]glucose into liver glycogen. Its changes were almost parallel to the changes in glycogen synthase activity. Progressive accumulation of liver glycogen that occurred in the fed state was associated with a proportional increase in glycogenic activity. Within 4 h after the cessation of food intake, glycogenic activity showed a precipitous fall from the peak to its nadir without significant changes in glycogen content. Meanwhile, the glucose concentration in the portal vein decreased. Upon further development of fasting, glycogenic activity displayed a progressive regain, reciprocally as glycogen contents gradually decreased. The precipitous fall of glycogenic activity during the transition from the fed to fasted states was associated with a transient increase in plasma glucagon, and was partly overcome by the injection of anti-glucagon serum. It is concluded that the fall of portal venous concentration of glucose and secretion of glucagon act as a signal to initiate liver glycogen metabolism characteristic of the fasted or postabsorptive state.

Animals↗
PubMed1980

Anomalous plasma cyclic AMP responses to glucagon in patients with liver disease.

The purpose of the present study is to show anomalies of the plasma cAMP response of patients with hepatic disorders to a single injection of a low dose of glucagon (1 microgram/kg body wt). The response was markedly blunted in patients with liver cirrhosis and potentiated in patients with acute or chronic hepatitis. This glucagon test is, therefore, promising for development as a simple diagnostic means without undertaking liver biopsy to distinguish cirrhosis from chronic hepatitis.

Adult↗
PubMed1980

Changes in plasma cyclic nucleotides levels during various acute physical stresses.

Studies were performed with healthy volunteers to determine the effects of various stresses known to increase sympathetic nerve activity on the plasma concentration of cyclic AMP and cyclic GMP. Plasma cyclic AMP rose promptly in response to exercise; the elevation was completely abolished by a simultaneous injection of propranolol. Plasma cyclic GMP rose slightly after exercise; the elevation was completely abolished by a simultaneous injection of atropine. No significant changes occurred during tilting and cold pressor stress. The increase in plasma concentrations of cyclic AMP and cyclic GMP may serve as putative indices for beta-adrenergic, and cholinergic functions respectively during exercise of humans.

Adolescent↗
PubMed1980

Plasma cyclic nucleotide responses to insulin-induced hypoglycaemia and methacholine in patients with hyperthyroidism.

The effect of insulin-induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin-induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during methacholine-induced hypotension, was also enhanced in hyperthyroid patients. It is likely that beta-adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism.

Adolescent↗