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Biomedical subjects

M Ui

Publications and source records attributed to M Ui.

At least 307 records · Page 17Linked to original sources
PubMed1980

Changes in the concentration of cyclic nucleotides dependent on their antibodies in plasma.

In the process of immunization of rabbits with cyclic AMP or cyclic GMP, the plasma concentration of cyclic AMP or cyclic GMP was markedly elevated as the titer of the antiserum increased. The i.v. injection of anti-cyclic AMP or anti-cyclic GMP antiserum into rats or mice also caused a marked increase in the respective cyclic nucleotide in plasma. On the other hand, an injection with the antiserum did not cause any significant increase in urinary cyclic nucleotides. Therefore, the effect of the antiserum seems to be different from that of glucagon or carbamylcholine which increases cyclic AMP or cyclic GMP respectively in both plasma and urine. The injection of the antiserum, but not nephrectomy, caused a significant increase in plasma cyclic nucleotides in adrenalectomized rats. This made it unlikely that the antiserum-induced increase was due to the inhibition of urinary excretion. The plasma cyclic nucleotides, increased by an i.v. injection with the antiserum, servived enzymatic hydrolysis by phosphodiesterase in vitro; most of them proved to be bound to the antibody. It was concluded that the increases in plasma cyclic nucleotides in the process of cyclic nucleotide-immunization were mainly due to decreased metabolic clearance of plasma cyclic nucleotides.

Animals↗
PubMed1980

Improvement of diabetic symptoms of hereditary diabetic (KK) mice by a single injection with islet-activating protein (IAP).

Islet-activating protein (IAP) prepared from the culture medium of Bordetella pertussis cells was very effective in eliminating diabetic symptoms characteristic of hereditary diabetic KK mice over a long period of time. After a single injection of IAP (5 microgram/kg body wt) into KK mice, the non-fasting concentration of blood glucose was maintained nearly normal over 2 weeks, with a gradual return to the pre-IAP level 30 days later. During this period, glucose tolerance was normalized and only few animals excreted glucose in urine. The second injection of IAP to these diabetic mice caused a more prolonged restoration of normoglycemia. When KK mice had been injected with IAP, they responded to epinephrine and isoproterenol more readily than did ddY mice in increasing plasma insulin and glycerol.

Animals↗
PubMed1980

Effects of islet-activating protein (IAP) on blood glucose and plasma insulin in healthy volunteers (phase 1 studies).

Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. The active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP-action is characterized by enhancement of insulin secretory response to glucose and other stimulants. A single injection of IAP into spontaneous diabetes rats resulted in normalization of their glucose intolerance over a period of a month. Acute and chronic animal toxicity tests showed that LD50 of IAP was 127 micrograms/kg in mice and 144 micrograms/kg in rats. After these animal experiments, phase 1 studies were designed and undertaken to establish dosage, duration of action and other factors. IAP of 0.5 micrograms/kg or 1.0 micrograms/kg did not bring about any serious toxic or adverse effects in five volunteers. On the 4th day of a single injection of IAP, insulin secretory response was proved to be enhanced. Follow-up studies showed that the IAP-action continued over a month or at most two months. Two features of IAP, i.e., the enhancement of insulin secretory response and the long duration of the action, was confirmed in healthy persons as well as in animals. As expected, IAP has a strong antigenic reaction resulting in formation of IgG antibody and possibly IgE antibody. The antigenicity of IAP causes some hindrance to clinical usefulness. For avoidance of anaphylactic reaction, IAP should be given repeatedly with care. The problem concerning antigen-antibody reaction should be overcome as soon as possible before the clinical use of IAP as a medicament.

Adult↗
PubMed1979

Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose.

1. A trace amount of glucose labelled with 14C uniformly and with 3H at position 2, 3 or 6 was injected intravenously into starved rats to measure the turnover rate of blood glucose. 2. Reliable estimates were made based on the semilogarithmic plot of specific radioactivity of the glucose contained in whole blood samples taken from the tail vein. 3. Glucose turned over more rapidly in hyperthyroid and more slowly in hypothyroid than in euthyroid rats. The percentage contribution of glucose recycling (determined from the difference in replacement rates between [U-14C]glucose and [6-3H]glucose) to the glucose utilization increased on induction of hyperthyroidism. 4. Futile cycles between glucose and glucose 6-phosphate (determined from the difference between replacement rates of [2-3H]glucose and [6-3H]glucose) were activated and inactivated by induction of hyperthyroid and hypothyroid states respectively. 5. The hepatic content of glycogen was much lower in hyper- and hypo-thyroid than in euthyroid rats. The enhanced glucose production in hyperthyroid rats resulted from not only activationof hepatic gluconeogenesis but also diversion of the final product of gluconeogenesis from liver glycogen to blood glucose. In hypothyroidism, the inhibition of gluconeogensis led to suppression of both glucose production and glycogenesis in the liver.

Animals↗
PubMed1979

Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Minor role of endogenous insulin in thyroid-dependent changes in glucose turnover.

1. Rates and rate coefficients of glucose utilization and replacement (glucose turnover) as well as its recycling were determined in rats by using [U-14C]- and [2-3H]-, [3-3H]- or [6-3H]-glucose. 2. In euthyroid rats, the blood concentration of glucose was 1.5 times and its turnover rate was 2 times as high in the fed state as in the starved state; consequently the rate coefficient, a measure of the capacity of rats to utilize blood glucose, was also higher in the former than in the latter. 3. Induction of mild diabetes by streptozotocin exerted little influence on the content and turnover of blood glucose in the starved state, whereas it caused hyperglycaemia and a decrease in the rate coefficient after feeding. 4. Induction of hyperthyroidism caused increases in rates and rate coefficients of glucose turnover to substantially the same extent whether or not the plasma concentration of insulin was lowered by treatment with streptozotocin or injection with anti-insulin serum. 5. It is concluded that thyroid hormones are capable of enhancing glucose turnover in the starved state independently of endogenous insulin, which plays a significant role in increasing glucose utilization in the fed state.

Animals↗
PubMed1979

Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Relation of catecholamine actions to thyroid activity in controlling glucose turnover.

1. In euthyroid rats, treatment with reserpine of 6-hydroxydopamine, which deprived neuronal terminals of catecholamines, resulted in increases in rates and rate coefficients for blood glucose turnover in the starved states as determined by decay of [U-14C,6-3H]-glucose. Conversely, the injection of adrenaline or noradrenaline into starved euthyroid rats caused a marked decrease in rate coeeficients for glucose turnover. There was no change in the percentage glucose recycling under these conditions. 2. Adrenaline and noradrenaline caused more pronounced hyperglycaemia in hyperthyroid than in euthyroid rats owing to the greater activation of hepatic glucose production. 3. The increase in glucose turnover characteristics of hyperthyroidism was observed even after treatment with an alpha- or beta-adrenergic antagonist, showing the insignificant role of the balance between alpha- and beta-adrenergic receptors in the thyroid-dependent metabolic changes. 4. Rate coefficients for glucose turnover were not affected by reserpine treatment or catecholamine injections when rats had been rendered hyperthyroid. 5. Thus catecholamines are direct determinants of glucose-turnover rates in the starved state, and depend to some extent on the prevailing thyroid state.

Animals↗
PubMed1979

Islet-activating protein. Enhanced insulin secretion and cyclic AMP accumulation in pancreatic islets due to activation of native calcium ionophores.

The mechanism whereby "islet-activating protein" (IAP) purified from the culture medium of Bordetella pertussis potentiates insulin secretion was studied by experiments in vitro with islets of rats once injected with IAP (0.5 micrograms/100 g body weight, 3 days before killing) or with islets that had been exposed to IAP (0.1 to 100 ng/ml) for 24 h. The IAP treatment markedly enhanced insulin secretory responses and cAMP accumulation in islets, facilitated the efflux of 45Ca through the cell membrane, and abolished the alpha-adrenergic action of epinephrine (and somatostatin) to inhibit glucose-induced insulin release, cAMP accumulation, and 45Ca uptake. These effects of the IAP treatment were reduced when islets were incubated in a low calcium medium. Based on these results, it was concluded that IAP interacts directly but slowly with the islet B cell in such a manner as to render more calcium available to the stimulus-secretion coupling mechanism as a result of sustained activation of native calcium ionophores on the cell membrane.

Animals↗
PubMed1979

Effect of in vivo pretreatment of rats with a new protein purified from Bordetella pertussis on in vitro secretion of insulin: role of calcium.

Rats were injected once iv with an islet-activating protein (IAP), a new protein purified from the culture medium of Bordetella pertussis. Three days later, their pancreases were studied in vitro for insulin secretory responses. As with pertussis vaccine, pretreatment of rats with IAP was effective in enhancing insulin release from pancreas during perfusion or from islets during incubation in response to secretagogues such as glucose and glibenclamide. The alpha-adrenergic inhibition of insulin secretion induced by epinephrine was also reversed by the pretreatment with IAP. 3-Isobutyl-1-methylxanthine caused insulin release due to accumulation of cAMP. This 3-isobutyl-1-methylxanthine-induced insulin release during perfusion was enhanced in a Ca-containing perfusate, but was conversely reduced in a Ca-free perfusate by the IAP pretreatment. Upon the addition of Ca to the Ca-free perfusate, more insulin was released from pancreases of IAP-treated rats than from those of nontreated rats.

Animals↗
PubMed1978

The plasma cyclic AMP response to catecholamines as potentiated by phentolamine in rats.

Norepinephrine failed to increase plasma cyclic AMP when injected alone into fasted rats, in contrast with sharp increases elicited by isoproterenol, epinephrine or tyramine. In rats pretreated with 6-hydroxydopamine or cocain, however, there was significant increase in plasma cyclic AMP after norepinephrine injection, suggesting that the rapid neuronal catecholamine uptake was at least partly responsible for the lack of norepinephrine action. Phentolamine was very effective in enhancing the epinephrine-, norepinephrine- or tyramine-induced increase in plasma cyclic AMP but without effect on the isoproterenol-induced increase. Blockade of postsynaptic alpha-adrenoceptors, rather than of presynaptic receptors, is likely to be involved in the phentolamine potentiation, since it was even observed in rats treated with 6-hydroxydopamine or cocaine. A discussion is presented regarding the mechanism by which cyclic AMP generation is influenced by the alpha- and beta-adrenoceptor interaction on effector cell membranes.

Animals↗
PubMed1978

Increases in plasma cyclic AMP dependent on endogenous catecholamines.

Administration of tyramine (with or without phentolamine) as well as induction of ether anesthesia or insulin hypoglycemia caused a sharp increase in plasma cyclic AMP in rats. Based on the findings that the treatment of rats with reserpine, 6-hydroxydopamine, cocaine or propranolol totally abolished tyramine-induced increases in plasma cyclic AMP, it was concluded that catecholamines released from sympathetic neuronal terminals by tyramine could activate adenylate cyclase via the stimulation of postsynaptic beta-adrenoceptors. In contrast, catecholamines secreted from adrenal medulla were largely responsible for the increase in plasma cyclic AMP induced by ether anesthesia; whereas glucagon, in addition to adrenal catecholamines, played a significant role in hypoglycemia-induced increases in plasma cyclic AMP. Assay of plasma cyclic AMP following these stimuli is very promising as a test for adrenergic activities in experimental and clinical studies.

Animals↗
PubMed1978

Plasma cyclic GMP: response to cholinergic agents.

S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5--10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the plasma concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats.

Acetylcholine↗
PubMed1978

Islet activating protein (IAP) derived from the culture supernatant fluid of Bordetella pertussis: effect on spontaneous diabetic rats.

The early phase of insulin secretion to an oral glucose load was blunted in spontaneous diabetic rats. The blunted insulin secretion was associated with markedly impaired glucose tolerance. A single injection of the islet activating protein (IAP), a protein derived from the culture medium of Bordetella pertussis, into the spontaneous diabetic rats normalised glucose tolerance. The increase in insulin response to glucose was an important contributing factor to the improvement of glucose tolerance. This curative effect of the IAP on the diabetic state was of long duration; glucose tolerance remained virtually normal over a period of one month in the diabetic rats. Perfusion of the isolated pancreas of the diabetic rats pretreated with IAP showed an increase in insulin response to glucose and loss of suppression of glucagon secretion by noradrenaline.

Animals↗