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M Ui

Publications and source records attributed to M Ui.

At least 325 records · Page 18Linked to original sources
PubMed1978

Biological properties of islets-activating protein (IAP) purified from the culture medium of Bordetella pertussis.

The biological activities were studied of a new protein, islets-activating protein (IAP), purified from the culture medium of Bordetella pertussis. Rats injected intravenously with 1 microgram of purified IAP exhibited markedly enhanced insulin secretory responses to glucose, glucagon, epinephrine, and sulfonylureas over a period from 3 to 10 days after the injection. The degree and duration of the enhancement were proportional to the dose of IAP; the maximal effect induced by 1-2 microgram of IAP persisted for as long as 2 months. There was a highly significant correlation between the enhancement of insulin secretion and suppression of epinephrine hyperglycemia over a wide range of doses of IAP, indicating that suppression of epinephrine hyperglycemia resulted from hypoglycemic action of insulin secreted in response to epinephrine challenge. Additional actions of IAP were observed in mice; mice treated with higher doses of IAP showed symptoms were observed when lower doses of IAP were injected into mice. Thus, it is concluded that IAP is a protein primarily possessing a unique action to potentiate insulin secretory responses of experimental animals to nutritional and hormonal stimuli.

Animals↗
PubMed1978

Subunit structure of islets-activating protein (IAP), a new protein isolated from the culture media of Bordetella pertussis.

The subunit structure was studied of islets-activating protein (IAP), a new protein recently isolated from the culture media of Bordetella pertussis and possessing a unique action, i.e., potentiating insulin secretory responses of animals, IAP dissociated into three subunits, F-1, F-2, and F-3, when incubated in 8M urea. Three subunits isolated by chromatography on CM-Sepharose and DEAE-Sepharose columns showed different molecular weights (F-1: 44,000, F-2: 20,000, F-3: 11,000) and different isoelectric points, but similar amino acid compositions. The F-1 subunit consisted of two polypeptide chains linked by S-S bonding(s), while the F-2 and F-3 subunits were single-chain peptides. These subunits, none of which was biologically active alone, associated upon incubation for 2 h at 37 degrees C and regained biological activities after association only when the F-3 subunit was present in the association product. Thus, the F-3 subunit was essential, and the F-1 and F-2 subunits were permissive, for the development of IAP activity in animals.

Amino Acids↗
PubMed1978

Formation of biologically active protein from the subunits of islets-activating protein (IAP), a new protein isolated from Bordetella pertussis.

Based on the finding reported in the preceding paper (Kanbayashi, et al.: J. Biochem) that subunits of islets-activating protein (IAP), a new protein purified from the culture media of Bordetella pertussis, were inactive as such, but regained the original biological activities when recombined, the conditions required for recovery of the biological activities were studied. Essentially the same biological activities as the native IAP were recovered when the smallest subunit, F-3, was incubated with one of the other subunits, F-1 and F-2, at a pH of around 7, at temperatures below 30 degrees C and for longer than 12 h. During the incubation, association products were formed which were isolated by gel filtration as homogenous proteins that consisted of two subunits probably in a molar ratio of 1 : 1. The native IAP (consisting of two IAP subunits including F-3) were equipotent in enhancing insulin secretory responses, in inhibiting epinephrine-induced hyperglycemia, in inducing leukocytosis and in increasing histamine sensitivity in experimental animals.

Animals↗
PubMed1978

Adrenergic modulation of insulin secretion in vivo dependent on thyroid states.

Insulin secretory responses via adrenergic mechanisms were studied in vivo with hyperthyroid rats prepared by daily injections with thyroxine and with rats rendered hypothyroid by the addition of methylthiouracil in the drinking water. Isoproterenol, a beta-adrenergic agent, caused hyperinsulinemia in hyperthyroid rats more markedly than in euthyroid rats, but failed to induce hyperinsulinemia in hypothyroid rats. The isoproterenol-induced hyperinsulinemia was abolished by a beta-adrenergic receptor blocker in hyperthyroid as well as in euthyroid rats. The glucose-induced hyperinsulinemia was enhanced in hyperthyroid, was not essentially affected in euthyroid, and was inhibited in hypothyroid rats, by an alpha- and beta-adrenergic agent such as epinephrine. It is concluded that the relative function of alpha- to beta-adrenergic receptors responsible for the pancreatic secretion of insulin is dependent on the thyroid state; beta-adrenergic actions are predominant over alpha-actions in hyperthyroidism and vice versa in hypothyroidism.

Animals↗
PubMed1978

Glucose load diverts hepatic gluconeogenic product from glucose to glycogen in vivo.

Intravenous or oral administration of concentrated glucose solution into fasted rats simultaneously injected with 14C-bicarbonate resulted in an inhibition of [14C]glucose release into the blood and in an accelerated [14C]glycogen formation associated with glycogen synthetase activation and phosphorylase inactivation in the liver. The specific activity of glycogen was much higher than that of blood glucose after the glucose load, indicating that glycogen originated from gluconeogenesis rather than blood glucose. These metabolic changes induced by the glucose load were not mediated by endogenous insulin because they were observed to the same extent in rats treated with anti-insulin serum. However, they were mostly, if not totally, abolished by adrenalectomy, which suppressed gluconeogenesis and glycogenesis. Glucose tolerance was markedly impaired not only by anti-insulin serum, which inhibits peripheral glucose utilization, but also by adrenalectomy, which affects hepatic metabolism. It is concluded that a glucose load diverts the final product of hepatic gluconeogenesis from blood glucose to liver glycogen; these metabolic changes in the liver are an important determinant of glucose tolerance.

Administration, Oral↗
PubMed1977

An involvement of alpha-adrenergic stimulation in exercise-induced hypoglycemia.

Hypoglycemia developed in fasted rats during forced swimming. This hypoglycemia was mostly abolished by phentolamine, an alpha-adrenolytic agent, or by hexamethonium; was potentiated by propranolol, a beta-adrenolytic agent, of by 5-methoxyindole-2-carboxylic acid, a gluconeogenic inhibitor; and was not affected by anti-insulin serum. The turnover rate of blood glucose estimated from the decay curve of blood [14C]glucose increased significantly during exercise. There was a slight but significantly increase during exercise in the transfer of 3-O-methyl-[14C]glucose into muscle and adipose tissues, when it was corrected for by [3H]mannitol transfer to the same tissues. It is concluded that the alpha-receptor-mediated action of endogenous catecholamine stimulates peripheral glucose utilization leading to hypoglycemia during exercise. The action of alpha- and beta-adrenergic mechanisms, directly on peripheral tissues or via insulin secretion, in fine regulation of blood glucose level is discussed.

Animals↗
PubMed1977

Hypoglycemia induced by alpha-adrenergic stimulation during alkalosis.

Hypoglycemia developed during respiratory alkalosis in fasted rats. This hypoglycemia was markedly potentiated by the simultaneous injection of inhibitors of hepatic gluconeogenesis or a beta-adrenergic blocking agent; was not influenced by anti-insulin serum; was attenuated by hexamethonium; and was abolished by an alpha-adrenergic blocking agent. The rate of removal of injected glucose by peripheral tissues increased during alkalosis in insulin-deficient rats. The uptake of [14C]-glucose by the adipose tissue in vivo, which is stimulated by a very minute amount of insulin, was also stimulated during alkalosis whether or not the circulating insulin was neutralized with anti-insulin serum. It was concluded that, in alkalotic rats, blood glucose is rapidly utilized by peripheral tissues dependent on alpha-adrenergic stimulation, but without mediation of insulin and that this leads to development of hypoglycemia.

Alkalosis, Respiratory↗
PubMed1977

Spontaneous recovery from streptozotocin-induced diabetes in rats pretreated with pertussis vaccine or hydrocortisone.

Following the intravenous injection of streptozotocin into rats, postprandial hyperglycaemia was sustained from 24 hours over a subsequent period of some weeks and the rats were glucose intolerant. When streptozotocin was similarly injected into pertussis-sensitized or hydrocortisone treated rats, the postprandial hyperglycaemia observed at 24 hours did not persist, but showed a progressive decline until near normoglycaemia was obtained a week later. These animals manifested normal glucose tolerance one week after streptozotocin. Thus, a spontaneous recovery from streptozotocin-induced diabetes occurred under these conditions. This spontaneous recovery from diabetes was associated with hyperinsulinaemia in the fed state.

Animals↗
PubMed1977

Increased absorption of iodochlorhydroxyquin by rat intestine in the presence of solubilizing agents.

The intestinal absorption of iodochlorhydroxyquin (clioquinol) by the rat was studied by determining the radioactivity in the bile, blood and several organs 90 min after direct application of 125I-labeled clioquinol into the duodenum. The addition of solubilizing agents such as carboxymethyl-cellulose and lauryl sulfate to clioquinol preparation markedly enhanced the intestinal absorption of the drug in either the presence of absence of bile secretion which, by itself, increased the drug absorption. Possible significance of the enhanced absorption of clioquinol by solubilizing agents in the etiology of subacute myelo-optic neuropathy (SMON) in Japan is discussed.

Animals↗
PubMed1977

Tracer kinetic analysis of Cori cycle activity in the rat: effect of feeding.

Turnover rates of blood glucose and lactate, along with the rates of their interconversion, were calculated from changes of their specific activities in rats infused with [U-14C] glucose and [U-14C] lactate based on a simple flux model of the Cori cycle. In the fasted state, most (75%) of the glucose metabolized was converted to lactate, whereas only a small fraction (35%) of the lactate metabolized was converted to glucose. Of the glucose metabolized, 27% returned from the lactate pool to the glucose pool. Feeding stimulated the outflow of glucose carbon from the Cori cycle via the action of secreted insulin. Insulin-induced stimulation of blood glucose removal was associated with increased glucose production, whereas anti-insulin serum-induced stimulation of glucose production was associated with increased glucose removal. It is argued that a "compensatory" mechanism independent of insulin and epinephrine might be in operation to minimize the glycemic changes that would otherwise occur in response to drastic metabolic changes.

Animals↗
PubMed1977

Activation of the Cori cycle by epinephrine.

The effect of epinephrine on Cori cycle activity has been studied by a tracer kinetic technique. The subcutaneous injection of epinephrine into fasted adrenodemedullated rats activated gluconeogenesis and increased glucose utilization. Most of the glucose utilized in epinephrine-treated rats was converted to lactate, and the conversion to the metabolites other than lactate was markedly suppressed by epinephrine. As a result, not only hyperglycemia and hyperlactacidemia developed, but also the contribution of the Cori cycle to glucose metabolism increased after epinephrine. The glucose-alanine cycle, which is roughly one-third as active as the Cori cycle, was only slightly activated by epinephrine. No evidence was obtained, in vivo and in vitro, for the increased formation of lactate from muscle glycogen which decomposed in response to epinephrine. It is suggested that, in epinephrine-treated rats, blood glucose was converted to blood lactate predominantly while muscle glycogen selectively yielded the metabolites other than blood lactate. This suggests compartmentalization of glycolytic pathway in the peripheral tissues of epinephrine-treated rats.

Adrenal Medulla↗
PubMed1977

Perfusion of the pancreas isolated from pertussis-sensitized rats: potentiation of insulin secretory responses due to beta-adrenergic stimulation.

In order to study the mechanism by which pertussis-sensitized rats showed enhanced insulin secretory responses to various secretagogues (Sumi, T., and M. Ui, Endocrinology 97: 352, 1975), pancreases of rats receiving a single injection of Bordetella pertussis cells 3 days before were perfused with Krebs-Ringer solution, and release of insulin therefrom was compared with that from the pancreases of normal rats. Much more insulin was released from the pancreas of the pertussis-sensitized rat than from the pancreas of the normal rat in response to glucose, arginine, glibenclamide and 3-isobuty-l-methylxanthine. The inhibition of insulin secretion caused by epinephrine, norepinephrine or phenylephrine via alpha-adrenergic receptors in the pancreas of normal rats was no longer observable with the pancreas from pertussis-sensitized rats. Instead, the addition of epinephrine with or without phentolamine gave rise to a marked secretion of insulin from the pancreas of pertussis-sensitized rats which was prevented by propranolol. It is concluded that a single injection of B. pertussis into rats results in a sustained modification of insulin secretory processes in the pancreatic beta-cells in such a manner as to favor insulin secretory responses to beta-adrenergic stimulation and other secretagogues.

Animals↗