Biomedical subjects

Y Akanuma

Publications and source records attributed to Y Akanuma.

At least 163 records · Page 9Linked to original sources

PubMed1985

Effect of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake in mouse pancreatic acini.

The effects of antigastrin (SC-15396) on amylase release and 2-deoxyglucose uptake were studied in dispersed acini from mouse pancreas. Antigastrin at concentrations between 0.5 and 2 mM inhibited cholecystokinin (CCK)-stimulated amylase release and 2-deoxyglucose uptake in a dose-dependent fashion. Antigastrin at concentrations between 0.5 and 2 mM inhibited carbachol-stimulated amylase release and 2-deoxyglucose uptake as well. In addition, the drug (2 mM) inhibited bombesin-stimulated amylase release and 2-deoxyglucose uptake. In contrast, the stimulation of amylase release by Ca2+ ionophore A23187 was not inhibited by antigastrin. The results, therefore, suggest that antigastrin nonselectively inhibits the actions of these secretagogues probably at their receptor sites.

Amylases↗

PubMed1985

Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia.

Familial hyperproinsulinemia is characterized by the accumulation of proinsulin-like material (PLM) in the plasma of affected patients. This disorder is inherited in an autosomal dominant fashion. The accumulation of PLM is thought to be due to the impaired conversion of proinsulin to insulin. Although PLM has been suggested to have an amino acid substitution, it has been impossible to locate and identify a substituted amino acid, due to the difficulty in isolating sufficient amounts of PLM from plasma samples. Therefore, we analyzed leukocyte DNA from one member of a proinsulinemic family, and we found a point mutation that changed guanine to adenine in the insulin gene. This transition implies that a substitution of histidine for arginine has occurred at amino acid position 65. Furthermore, it indicates that arginine at 65 is essential for the conversion of proinsulin to insulin. Our results suggest a novel mechanism by which disease can be incurred: a heritable disorder can result from a posttranslational processing abnormality caused by a point mutation.

Amino Acid Sequence↗

PubMed1985

Characteristics of insulin receptors and insulin action in human myelogenous leukemia cell line K-562.

Specific binding sites for insulin have been identified and characterized for the human erythroleukemia cell line K-562. The binding of [125I]-insulin to the cells increased as a function of time, reaching a maximum at 20 min when incubation was performed at 37 degrees C. The binding of [125I]-insulin was dose-dependently inhibited by insulin or proinsulin. Scatchard plot of the binding data was curvilinear, and the number of insulin receptors was approximately 39,000. Insulin at concentrations of 0.05-10.0 ng/ml stimulated CO2 production and DNA and protein synthesis in K-562 cells in a dose-dependent manner, indicating that the insulin binding sites are functionally important in mediating these biochemical events induced by insulin. Maximal insulin responses were elicited at concentrations of less than 5 ng/ml, when (at most) 10% of the insulin receptors were occupied. After binding to the cells, [125I]-insulin was degraded in a time- and temperature-dependent manner. As reported for other types of cells, unlabeled insulin also downregulated insulin receptors in K-562 cells. When the cells were incubated with 1 X 10(-7) M unlabeled insulin for 24 h, the number of insulin receptors decreased by 50% without a change of affinity. K-562 cells may be useful in studying the role of insulin receptors in cell functions induced by insulin.

Carbon Dioxide↗

PubMed1985

Relation of blood glucose levels to the changes in plasma levels of various hydrolytic enzymes in diabetic patients.

Plasma levels of various hydrolytic enzymes in diabetic patients, as diagnosed by their blood glucose levels, were compared with those of control subjects. Most of the levels of the aminopeptidase activities examined were significantly increased, while those of angiotensin-converting enzyme (ACE) and esterase decreased, in diabetic patients. The results of multivariate analysis suggest that the increased aminopeptidase activities are related rather to secondary organ lesions than to the primary pancreatic lesion. It seems that the blood glucose level is not necessarily a good indicator of metabolic abnormalities underlying this pathological condition.

Acetylcholinesterase↗

PubMed1985

Normotriglyceridemic abetalipoproteinemia in infancy: an isolated apolipoprotein B-100 deficiency.

The plasma lipoproteins of a 1-year-old Japanese infant were studied because of malnutrition, severe decrease in plasma lipid level, and acanthocytosis. Plasma lipoprotein analysis revealed that low-density lipoproteins were deficient; however, low levels of triglyceride-rich lipoproteins were found in the plasma. On sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis, apoprotein B-48 and a faint band corresponding to apoprotein B-100 were detected in the lipoprotein fraction of density less than 1.006 g/mL when the infant was 6 months old. Apoprotein B-48 was more clearly detected after 1 year, but the band corresponding to apoprotein B-100 on the sodium dodecylsulfate gel electrophoresis had disappeared. The apoprotein B-48 content of the fraction with density less than 1.006 g/mL was about 0.05 to 0.3 mg/dL. The patient's lipoproteins consisted mainly of high-density lipoproteins. These results suggest that the disorder in this patient is caused by apoprotein B-100 deficiency.

Abetalipoproteinemia↗

PubMed1984

Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats.

It has been documented that streptozotocin-induced diabetes in rats is associated with diminished effects of insulin despite increased insulin binding to its receptor. This paradox led us to examine whether any alterations of insulin receptor-kinase activities occur in this type of insulin resistance. Insulin binding capacity/mg of protein of solubilized, wheat germ agglutinin-purified preparations from livers was increased by 1.8-fold in the streptozotocin (65 mg/kg) diabetic rats. This increase was associated with a parallel increase in receptor protein as measured by an immunoblotting method using anti-insulin receptor antibody. Moreover, no apparent change was observed in the stoichiometry of alpha and beta subunits of the insulin receptor between diabetic and control rats. Insulin-stimulated (10(-7) M) phosphorylation of the beta subunit of the insulin receptor was decreased by 40% in diabetic rats when equal quantities of insulin binding capacity were compared. Phosphorylation of an exogenously added synthetic peptide (similar in sequence to the tyrosine phosphorylation site in pp60src) by the insulin receptor-kinase was also decreased by 25% in diabetic rats. These abnormalities were partially restored by in vivo insulin treatment. These data suggest that diminished insulin receptor autophosphorylation and kinase activity could provide a possible mechanism for the "post-binding insulin resistance" in diabetic rats.

Animals↗

PubMed1984

Risk factors for worsening to diabetes in subjects with impaired glucose tolerance.

In a 5-12 year follow-up study of 288 subjects with impaired glucose tolerance after a 100-g glucose load, 48 worsened to overt Type 2 (non-insulin-dependent) diabetes with the elevation of fasting blood glucose. The initial level of blood glucose was a major predictor of subsequent worsening to diabetes. In addition, subjects with a lower insulin response to glucose showed a higher incidence of worsening to the disease, irrespective of blood glucose levels. Multivariate analysis indicated that a diminished insulin response and a high maximal body weight index, as well as a high level of fasting and 2-h glucose values at the initial 100-g oral glucose tolerance test were significant independent risk factors for the development of diabetes in Japanese subjects.

Adult↗

PubMed1984

In vitro and in vivo effect of proglumide on cholecystokinin-stimulated amylase release in mouse pancreatic acini.

The effect of proglumide on cholecystokinin (CCK)-stimulated amylase release was studied in vitro and in vivo in dispersed acini from mouse pancreas. In an in vitro study, proglumide at concentrations between 0.3-10 mM inhibited CCK-stimulated amylase release dose-dependently, while proglumide did not influence the basal amylase release at concentrations between 0-3 mM. Dose-response curves to CCK for amylase release shifted to the right with increase in proglumide concentration. This inhibition by proglumide was reversible. In addition, the effect of proglumide was selective for CCK and its related peptide, and this drug did not inhibit other secretagogues such as carbachol or gastrin releasing peptide in mouse acini. In contrast to its inhibitory effect in vitro, in vivo administration of proglumide (500 mg/kg/day, i.p., for 5 days) to mice did not cause the rightward shift of the dose-response curve to CCK for amylase release from dispersed acini.

Amylases↗

PubMed1984

Alteration of beta-cell function in different diabetic states.

To assess the effects of metabolic control upon beta cell function in diabetes, pro-insulin and insulin were determined following gel-filtration of plasma at two time points in each three diabetic patients, once when the metabolic state was severely deranged and again after the metabolic state had improved after therapy. Before therapy, proinsulin concentration were 30 pM (as IRI), both fasting and at 2 hours after an oral glucose load. These values did not change with treatment. Insulin concentrations were 22 pM at both time points before therapy. With treatment, plasma insulin increased 2-fold at fasting and 7-fold at 2 hours after oral glucose. These results suggest an exhaustion of the insulin pool in beta cells during severe metabolic decompensation of diabetes, a condition which may be reversed by correction of the metabolic states of the patients with proper therapy.

Acromegaly↗

PubMed1984

Plasma lipoproteins in streptozotocin-diabetic rats, after Triton WR-1339 treatment.

In an attempt to examine whether the VLDL secreted by diabetic rats may be different from that by normal rats, plasma obtained after Triton WR-1339 treatment was analyzed. After Triton treatment, a marked increase in plasma triglyceride levels with lesser increases in cholesterol and phospholipids was observed in both diabetic and control rats. The degree of such increases was almost equal between two groups of rats. The large increases in plasma lipid levels presumably reflect the increase in plasma VLDL fraction. The lipid composition of VLDL of diabetic rats was very similar to that of normal controls. The LDL fraction of diabetic rats was low in its contents of both cholesterol and phospholipids compared with that of normal controls. The composition of IDL and HDL in diabetic rats was similar to that of controls. From these data, we suggest that the VLDL of diabetic rats secreted under basal fasting condition is not different in its lipid composition as well as in amounts from that of controls.

Animals↗

PubMed1984

Reciprocal changes of plasma apo AI and apo E levels in streptozotocin-induced diabetic rats.

Amounts of plasma lipids, apolipoprotein AI (apo AI) and apolipoprotein E (apo E) were measured in streptozotocin-induced diabetic rats. Plasma triglyceride and cholesterol levels of diabetic rats were not significantly different from those of control rats. Plasma apo AI levels of diabetic rats were significantly higher than those of control rats (78.2 +/- 29.3 vs 27.2 +/- 3.4 mg/dl, P less than 0.001), while plasma apo E levels of diabetic rats were significantly lower than those of control rats (4.2 +/- 1.0 vs 13.9 +/- 5.3 mg/dl, P less than 0.001). Insulin treatment (12U/day) of diabetic rats decreased plasma apo AI levels significantly (treated: 32.8 +/- 3.4, untreated: 48.7 +/- 6.2, control: 28.5 +/- 2.4 mg/dl) and normalized plasma apo E levels (treated: 16.1 +/- 1.7, untreated: 5.4 +/- 0.7, control: 15.8 +/- 1.3). Insulin injection (4U/day) to normal rats did not cause any changes in both plasma apo AI and apo E levels. The data indicate that diabetes is not always accompanied by hyperlipidemia, however this inevitably carries apoprotein abnormalities characterized by the high plasma apo AI and low apo E levels, which are reversible with insulin treatment. The changes in the levels of plasma apo AI and apo E could be related to the development of atherosclerosis in diabetes.

Animals↗

PubMed1984

Effects of plasma infusion on plasma lipids, apoproteins and plasma enzyme activities in familial lecithin: cholesterol acyltransferase deficiency.

The siblings presented here are the third family found in Japan with familial LCAT deficiency. Their post-heparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured selectively by an immunochemical method. Plasma triglyceride levels were elevated, and post-heparin plasma lipoprotein lipase was decreased only in a patient with nephropathy, while hepatic triglyceride lipase activities were within reference limits in both patients. The plasma concentrations of apo A-I, apo A-II, and apo B were reduced in both patients. On the other hand, the plasma concentration of apo E was markedly increased. Enzyme replacement therapy by plasma transfusion in the propositus resulted in marked improvement of deranged compositions of triglyceride-rich lipoproteins. Also, improvement of the plasma apo E concentration was demonstrated, while the improvement of post-heparin lipase did not occur. These results suggest that LCAT may play an important physiological role in triglyceride metabolism as well as in cholesterol metabolism.

Apoproteins↗

PubMed1984

New powerful insulin-like protein from human promyelocytic leukemia cells.

Potent insulin-like activity was found in the conditioned medium of human promyelocytic leukemia (HL-60) cells. The conditioned medium of HL-60 cells at high density stimulated [3H]glucose incorporation into lipids in rat adipocytes in a time- and dose-dependent manner. The dose-response curve for this factor was not parallel to that for insulin, and the maximal effect achieved was much greater than reached by insulin or multiplication-stimulating activity. Moreover, the maximal effect reached by either insulin or the conditioned medium was additive. The insulin-like activity was not suppressed in the presence of antiinsulin antibody. Insulin-like activity was not detectable by radioreceptor assay for insulin, suggesting that the factor does not act through the insulin receptor. The factor in the conditioned medium of HL-60 cells was heat stable and sensitive to trypsin. When the conditioned medium was subjected to gel filtration on a Sephadex G-100 column, the major part of insulin-like activity eluted in the position corresponding to an apparent molecular weight between RNAase and insulin markers. The remaining activity, approximately 10% of the total, appeared with a larger molecular weight species. On isoelectric focusing of the smaller molecular species, insulin-like activity was largely focused in the position corresponding to pI 7.8-8.2.

Adipose Tissue↗

PubMed1984

A study of serum free C-peptide responses to oral glucose load in diabetic patients: with special reference to types of diabetes and methods of treatment.

Serum free C-peptide immunoreactivities (serum free CPR) during a 100 g oral glucose tolerance test (OGTT) were measured in 21 patients with insulin-dependent diabetes mellitus (IDDM, with abrupt onset and ketosis-prone), 57 insulin-treated patients with noninsulin-dependent diabetes mellitus ( INIDDM , with gradual onset and not ketosis-prone), 39 oral hypoglycemic agent-treated patients with noninsulin-dependent diabetes mellitus ( ONIDDM ) and 9 healthy young men for control study. Although the fasting blood glucose value of the INIDDM group was not significantly different from that of the IDDM and ONIDDM groups, the free CPR response at each interval during OGTT in the INIDDM group was significantly higher than that in the IDDM group and lower than that in the ONIDDM group. The sum of serum free CPR during OGTT (sigma serum free CPR) was found to be negatively correlated to the duration of insulin treatment either in bivariate or multivariate analysis in INIDDM patients. Using 9.5 ng/ml as an index, all sigma serum free CPR values in the ONIDDM group were above this index, whereas all the values except one in the IDDM group were below it. The values in the INIDDM were scattered within the ranges of the other two groups. The insulinogenic index delta serum free CPR/delta blood glucose (30 min-fasting) of the ONIDDM group was significantly lower than that of normal subjects, although sigma serum free CPR values were not significantly different. The results indicate that: 1. Residual pancreatic B-cell function in INIDDM patients is lower than that in ONIDDM patients and is negatively correlated to the duration of insulin treatment in INIDDM patients. 2. Measuring serum free CPR may be a discriminative method for establishing insulin dependency in insulin-treated patients. 3. Impairment of early insulin secretion after the oral glucose load is a distinguished characteristic of diabetic patients.

Adolescent↗

PubMed1983

Abnormalities in plasma lipoprotein in familial partial lecithin:cholesterol acyltransferase deficiency.

Abnormalities in plasma lipoproteins from patients with familial partial lecithin:cholesterol acyltransferase deficiency were studied. In these patients the plasma cholesterol ester ratio was about 40% and plasma apolipoprotein B level remained within the normal range. The content of large-sized low-density-lipoproteins (LDL) was low. Apolipoprotein B-100 and B-48 were detected in very-low-density lipoproteins (VLDL) and LDL in patients' plasma. In patients' LDL, apolipoprotein B-48 was primarily present in large-sized particles. Apolipoprotein E and A-I were mainly detected in intermediate-sized LDL. High-density lipoproteins (HDL) were separated into three fractions by gel permeation chromatography. Large-sized HDL particles (150-200 A) including discoidal particles contained apolipoproteins, E, A-IV and A-I. The content of discoidal HDL was low and, on electron micrograph, rouleau-formed particles were rarely seen. Normal-sized HDL (80-100 A) contained apolipoproteins A-I and A-II and small-sized HDL (about 60 A) contained only apolipoprotein A-I. Although several lipoprotein abnormalities were similar to those in classical familial lecithin:cholesterol acyltransferase deficiency, remaining lecithin:cholesterol acyltransferase activity may, however, cause a lack of reduction of apolipoprotein B level, a low level of large-sized LDL and also a low level of discoidal HDL.

Adult↗

PubMed1983

Analysis of apolipoproteins B100 and B48 by sodium dodecyl sulfate polyacrylamide gradient gel electrophoresis.

Apolipoproteins B100 and B48 in human and rat plasma were studied by using sodium dodecyl sulfate (SDS) polyacrylamide gradient gel electrophoresis. On SDS gradient gel electrophoresis, human and rat apoprotein B100 co-migrated and had an apparent Mr equal 258,000 +/- 12,000. Human and rat apoprotein B48 had an apparent Mr equal 189,000 +/- 6,000. The molecular weight of human apoprotein B100 determined by sedimentation equilibrium analysis was 270,000 +/- 20,000, which was similar to the value determined by SDS gradient gel electrophoresis. However, on SDS polyacrylamide gel electrophoresis at constant concentration, the relative migration value of human apoprotein B100 was not constant when the concentration of polyacrylamide was changed. These results indicate that SDS gradient gel electrophoresis is more suitable for the analysis of apolipoprotein B's than ordinary SDS polyacrylamide gel electrophoresis.

Animals↗

PubMed1983

Effects of porcine gastrin-releasing peptide on amylase release, 2-deoxyglucose uptake, and alpha-aminoisobutyric acid uptake in mouse pancreatic acini.

The effects of synthetic porcine gastrin-releasing peptide (pGRP), a recently isolated gut hormone, were studied in isolated mouse pancreatic acini. pGRP was found to exert direct effects on amylase release, 2-deoxyglucose ( [3H] 2DG) uptake, and alpha-aminoisobutyric acid (AIB) uptake. The stimulatory effect of pGRP on amylase release was significant at 100 pM, and maximal at 1 nM. Higher concentrations of pGRP exerted a smaller stimulatory effect on amylase release. pGRP also increased [3H]2DG uptake, exerting a detectable effect at 300 pM, and a maximal effect at 30 nM. In contrast to its stimulatory effect on amylase release and [3H]2DG uptake, pGRP inhibited AIB uptake. A significant inhibitory effect on AIB uptake occurred at 100 pM, and a maximal inhibitory effect occurred at 3 nM. Dose-response curves of pGRP for amylase release and AIB uptake were found to be biphasic. Bombesin was also found to stimulate amylase release with a biphasic dose-response curve in mouse acini. Both cholecystokinin (CCK) octapeptide and the cholinergic analog carbachol exerted similar effects in isolated mouse acini. However, the effects of pGRP were not inhibited by either dibutyryl cyclic guanosine 3',5'-monophosphate or atropine, whereas the effects of CCK octapeptide were inhibited by dibutyryl cyclic guanosine 3',5'-monophosphate and the effects of carbachol were inhibited by atropine. These results indicate that pGRP can mimic the biological effects of CCK and acetylcholine, but that its actions are probably mediated via a separate class of receptors in mouse acini.

Aminoisobutyric Acids↗

PubMed1983

Reduction of C-peptide secretion in noninsulin-dependent diabetic patients with long duration of insulin treatment.

We examined the responses of serum free C-peptide immunoreactivity (CPR) during a 100 g oral glucose tolerance test (OGTT) on diabetic patients undergoing different kinds and durations of treatment. None of the patients were ketosis-prone or had any history of nephropathy and they all developed diabetes when over the age of 30. The sigma serum free CPR (the sum of serum free CPR values during OGTT) of group A (duration of insulin treatment was less than 5 years, N = 10) was found to be higher than that of group B (duration of insulin treatment was 5 years or more, N = 10) (p less than 0.005). On the other hand, the sigma serum free CPR of group C (treatment with an oral hypoglycemic agent for less than 5 years, N = 9) was not statistically different from that of group D (treatment with an oral hypoglycemic agent for 5 years or more, N = 11). There were no statistical differences between group A and group B in age at onset, duration of diabetes, daily insulin dose, relative body weight index, serum creatinine or sigma BG (the sum of blood glucose values during OGTT). Just before the start of insulin treatment, there were no significant differences between the two groups in the following: 1. fasting blood glucose values (all 10 patients measured in group A and 9 patients in group B) 2. blood glucose and plasma immunoreactive insulin (IRI) responses (7 patients measured in group A and 6 in group B). Among those with plasma IRI measured on the previous occasion, sigma serum free CPR was found to be higher in group A than in group B (p less than 0.025) at the time of the present study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗