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Biomedical subjects

Y Akanuma

Publications and source records attributed to Y Akanuma.

At least 217 records · Page 12Linked to original sources
PubMed1978

The interaction of apolipoproteins with lecithin:cholesterol acyltransferase.

The rate of lecithin:cholesterole acyltransferase reaction was measured in a cholesterol-containing single bilayer lecithin vesicle system. ApolipoproteinA-I (apoA-I) activated the enzyme by itself; the other components of apolipoproteins of high density lipoproteins (HDL) (rho = 1.08--1.2 g/cm3), or rabbit serum gamma globulin inhibited the reaction. The reaction which was activated by pure apoA-I was strongly inhibited by anti-apoA-I antibody. Quantitative analysis of the results showed that the lecithin:cholesterol acyltransferase reaction was activated by the binding of apoA-I to the surface of lipid substrates. The rate of the lecithin:cholesterol acyltransferase-catalyzed reaction was strictly proportional to the surface density of apoA-I. The inhibition was due to the decrease of the amount of apoA-I on the lipid surface, either through competitive exclusion by apoA-II or by other proteins, or through specific extraction with antibody. The presence of components of apoHDL, other than apoA-I, prevented the inhibitory action of anti-apoA-I antibody.

Antigen-Antibody Reactions↗
PubMed1978

Insulin binding and glucose metabolism in adipocytes of streptozotocin-diabetic rats.

To investigate the mechanism of the cellular insulin insensitivity of diabetic rats, insulin binding, glucose transport, and glucose oxidation were studied in adipocytes from streptozotocin-diabetic rats. Increased insulin binding was found in cells from diabetic rats, and this was due to an increased number of insulin receptors rather than a change in receptor affinity. Basal and insulin-stimulated glucose oxidation was decreased in adipocytes from diabetic rats when the data are expressed in absolute terms or as percent increased above basal. Although the absolute rate of basal and insulin-stimulated glucose transport was decreased in adipocytes from diabetic rats, the percent increase above basal of insulin-stimulated glucose transport was not decreased. In conclusion, although the cellular insulin insensitivity exists in adipocytes from diabetic rats, the number of insulin receptors was increased, coupling between insulin receptors and the glucose transport system is intact in adipocytes from diabetic rats, and a defect in intracellular glucose metabolism rather than glucose transport plays a major role in the insulin insensitivity of adipocytes from diabetic rats.

Adipose Tissue↗
PubMed1978

Effects of antiinsulin receptor autoantibody on the metabolism of rat adipocytes.

We have studied the effects of the serum from a patient with an unusual form of diabetic syndrome with extreme insulin resistance on the metabolism of rat adipocytes in vitro. This serum and IgG fractions from it inhibited the [125I]insulin binding to isolated adipocytes and stimulated the 2-deoxyglucose uptake, glucose oxidation, and the incorporation of amino acids into protein. In addition, these fractions inhibited the lipolysis induced by beta 1-24 ACTH in isolated adipocytes. The insulin-like effects of this serum and the effects of insulin were not additive at their maximal concentrations. The inhibition of [125I]insulin binding was due to a decrease in receptor affinity rather than to a change in receptor number by Scatchard plot analysis. Both the inhibition of insulin binding and the insulin-like effects on rat adipocytes were neutralized by antihuman IgG. In addition, these insulin-like effects were abolished by trypsin treatment of adipocytes. These facts suggest that this serum has a circulating antibody directed at or near the insulin receptor itself and that this antibody mimics the insulin effect on rat adipocytes by binding to the insulin receptor in vitro.

Adipose Tissue↗
PubMed1978

Degradation and secretion of insulin in hepatic cirrhosis.

To clarify the mechanism of hyperinsulinism of hepatic cirrhosis, plasma insulin and C-peptide levels before and after oral glucose loads were measured in 34 patients with cirrhosis, 15 patients with chronic hepatitis, and 25 normal subjects. While plasma immunoreactive insulin (IRI) levels during oral glucose tolerance testing (OGTT) were significantly increased in cirrhotics, plasma immunoreactive C-peptide (CPR) levels were elevated slightly. The C-peptide to insulin ratio throughout OGTT was significantly smaller in cirrhotics than in normal subjects (P less than 0.01). A decreased hepatic insulin degradation rate has been suggested to one of the main causes of hyperinsulinism in hepatic cirrhosis. The ratio of the difference between basal and 30-min CPR values and basal and 30-min OGTT blood glucose values [delta CPR: delta BS(30)'] as well as the delta IRI: delta BS(30') ratio was significantly decreased in cirrhotics (P less than 0.01). These results indicate that insulin secretion in response to a glycemic stimulus is reduced in cirrhotics. Both the ratios of the sums of six IRS and CPR values of OGTT (sigma CPR: sigma IRI) and delta CPR: delta BS(30') and sigma CPR: sigma BS(30') were found in inverse relationship with indocyanine green retention rate in cirrhotics.

Adult↗
PubMed1978

Effects of anti-insulin receptor autoantibodies on the metabolism of human adipocytes.

We studied the effect of sera from two patients who had an unusual form of diabetic syndrome with extreme insulin resistance on the metabolism of human adipocytes in vitro. The IgG fractions from sera A and B, which were obtained from two patients (1 and 2) with insulin-resistant diabetes, inhibited [125I] insulin binding to human adipocytes and, at the same time, stimulated glucose oxidation and inhibited the lipolysis induced by levarterenol in human adipocytes. On the other hand, the IgG fraction from the C serum, which was obtained from patient 2 after her diabetic syndrome had completely disappeared as a result of immunosuppressive therapy, did not inhibit [125I] insulin binding to human adipocytes, stimulate glucose oxidation, or inhibit lipolysis in human adipocytes. These facts suggest that these IgG fractions bind to or near the insulin receptor of human adipocytes, that they exhibit their insulin-like effect by binding to the insulin receptor in vitro, and, furthermore, that they are responsible for the extremely insulin-resistant diabetes. However, the apparent discrepancy between the effects of these IgG fractions on man in vitro and in vivo is puzzling and needs to be explained.

Adipose Tissue↗
PubMed1977

Comparative effects of native insulin and insulin-dextran complexes on the metabolism of adipose tissue.

Insulin-dextran complexes have been prepared and their biological activities compared to that of native insulin. Complexes referred to as T-70 had a molecular weight of about 450 000, T-2000 being more than 2 million. Insulin-dextran T-70 was stable and no release of free insulin from the complex was observed upon its incubation with adipose tissue. Insulin-dextran T-70 mimicked the effects of native insulin upon adipose tissue metabolism. It also lowered blood sugar. These effects necessitated, on an insulin molar basis, concentrations of the complex that were 10-times greater than those needed for native insulin. Maximal concentrations of insulin complex T-70 or native insulin elicited similar quantitative effects. This suggested that when the concentration of insulin-dextran T-70 was high enough, the complex occupied a sufficient number of receptor sites to produce maximal stimulation of the tissue. In contrast, insulin-dextran T-2000 was barely effective, indicating that, probably due to its size, it was unable to reach receptor sites. The size, stability and metabolic effects of insulin-dextran T-70 observed in this study give additional support to the concept that insulin action is probably mediated via a series of events initiated at the level of the plasma membrane of adipocytes.

Adipose Tissue↗
PubMed1977

A new colorimetric method for the determination of plasma lecithin-cholesterol acyltransferase activity.

A new method has been developed to improve the linearity of the plasma lecithin-cholesterol acyltransferase reaction by adding synthetic dipalmitoyl lecithin sol to the incubation medium and subsequently measuring the change in free cholesterol content after incubation by a combined enzymatic method using cholesterol oxidase and peroxidase. The method was found to be simpler than other techniques such as gas-liquid chromatography or isotope methods and therefore may be suitable for the routine assays of plasma lecithin-cholesterol acyltransferase activities in clinical laboratories.

Acyltransferases↗
PubMed1977

Phosphatidylcholine substrate specificity of lecithin: cholestrol acyltransferase-in high density lipoproteins and in lipids dispersions.

Lecithin: cholesterol acyltransferase (LCAT) was more highly activated by apolipoprotein A-I (apoA-I) with dimyristoyl phosphatidylcholine (DMPC) than with dilinoleoyl phosphatidylcholine (DLPC) when lipid dispersion of cholesterol and each phosphatidylcholine was used as a substrate. When the enzyme reactions were activated by whole apolipoproteins of high density lipoproteins (HDL), DLPC was more available to the LCAT reaction than DMPC with high concentrations of apoHDL in an incubation mixture. However, no detectable enzyme reaction was observed with dipalmitoyl phosphatidylcholine (DPPC) under both conditions. On the other hand, all of these phosphatidylcholines acted as substrates of LCAT when they were incorporated into HDL coupled to Sepharose. The order of their relative reactivities to cholesterol was DMPC, DPPC, AND DLPC under the conditions used.

Apolipoproteins↗
PubMed1977

Effects of fasting and refeeding of insulin receptors and glucose metabolism in rat adipocytes.

To investigate the mechanism of insulin insensitivity during fasting and hyperresponsiveness to insulin after refeeding, insulin binding, 2-deoxyglucose uptake and glucose oxidation were measured in adipocytes from three groups of rats: control, 48 h fasted, and 48 h refed after 48 h fasting. In 48 h fasted rats, fat cell diameters were decreased to five-sixths of that of the controls and plasma insulin levels were decrease to less than half of the controls; however, after 48 h refeeding, these parameters were restored to normal. In adipocytes from fasted rats, insulin binding was increased but insulin-stimulated 2-deoxyglucose uptake glucose oxidation were significantly decreased as compared to that of the controls. In adipocytes of refed rats, insulin bindings was slightly increased as compared to the controls, accompanied by a slightly decreased 2-deoxyglucose uptake and completely restored glucose oxidation. Conclusions from these studies are that both disorders in coupling of insulin-receptor complexes to glucose transport systems and intracellular glucose metabolism play major roles in the insulin insensitivity of adipocytes from fasted rats, whereas, in adipocytes from refed rats, intracellular glucose metabolism, rather than glucose transport, is mainly involved in restoring insulin sensitivity.

Adipose Tissue↗
PubMed1977

A method for incorporating labeled lacithin into serum low density lipoproteins in vitro.

A sonicated dispersion of [14C]lecithin was incubated with high density lipoproteins (HDL) coupled to Sepharose. After washing the gels thoroughly with a buffer, the gels were incubated with low density lipoproteins (LDL); [14C]lecithin was transferred from the sonicated dispersion via HDL-Sepharose to the LDL. The LDL fraction thus prepared showed no contamination with lecithin dispersion or HDL. The lecithin:cholesterol acyltransferase (LCAT) reaction could be completely inhibited during preparation, and the net recovery of radioactivity in LDL was 16% of that of the original lecithin dispersion. The [14C]lecithin in the washed HDL-Sepharose was shown to be a substrate of the LCAT reaction in vitro.

Carbon Radioisotopes↗
PubMed1976

Effects of hyperosmolarity on the cyclic AMP concentration and lipolysis of the adipocyte stimulated by adrenocorticotropic hormone.

The effects of ACTH on 3',5'-cyclic AMP (cAMP) levels and lipolysis were examined on isolated adipocytes incubated in either isosmolar or hyperosmolar media. The ability of ACTH to induce intracellular cAMP accumulation was greatly enhanced by incubating cells in hyperosmolar sucrose (100 to 400 mM) solutions. Hyperosmolar solutions prepared by the addition of either NaCL, glucose or mannitol enhanced the ACTH effect on cAMP to the same extent as did the hyperosmolar sucrose solution, but hyperosmolar urea solutions did not have such an effect. The effect of hyperosmolarity was shown only in cells stimulated by lipolytic hormones, and the effects were still evident in the presence of high concentrations of theophylline, indicating the effect of hyperosmolarity is to facilitate hormone action on the receptor-coupler system of the adipocyte membrane. The action of glucagon on cAMP was augmented much less than the actions of ACTH and isoproterenol. Basal as well as ACTH or exogenous cAMP stimulated lipolysis was lower in hyperosmolar sucrose solutions. Some mechanism by which hyperosmolarity interferes with the metabolic sequence beyond the accumulation of cAMP was suggested.

Adipose Tissue↗