Search PubMed⌕ Search

Biomedical subjects

Y Akanuma

Publications and source records attributed to Y Akanuma.

At least 199 records · Page 11Linked to original sources

Reduced levels of plasma 1,5-anhydroglucitol in diabetic patients.

Anhydroglucitol in human plasma was studied by high pressure liquid chromatography, which was employed to simplify sampling procedures for the polyol assay and to avoid enzymatic treatment of the plasma for removal of glucose. Polyols in the column effluent were assayed by a flow fluorometric method, which involved two continuous successive reactions; periodate oxidation and the Hantzsch reaction. Plasma, 1 ml each, from 55 diabetic and 18 control subjects was deproteinized, concentrated, and subjected to the liquid chromatography. The results of this analysis indicated that the plasma anhydroglucitol level showed an inverse correlation with the plasma glucose level, while the correlation of glycerol and glucose levels was obscure.

Blood Glucose↗

Insulin secretory responses in patients with glucose intolerance due to extra-pancreatic causes. Comparison with idiopathic diabetes mellitus.

Insulin responses during 100 g glucose tolerance tests (GTT) were compared between three groups of patients with varying degrees of glucose intolerance. Patients who had no disease known to be associated with secondary diabetes were classified as patients with idiopathic diabetes mellitus. Those whose present and past fasting blood glucose (FBG) exceeded 140 mg/100 ml were assigned to Group A, and the rest of the patients to Group B. Group C included patients with liver disease, thyrotoxicosis, or myocardial infarction, or those treated with corticosteroids or who had undergone gastrectomy. Patients in Group A were found to have consistently subnormal insulin responses whether glucose tolerance was normal (i.e. previous abnormality of glucose tolerance), borderline, or diabetic. In contrast, patients in Group C without fasting hyperglycemia had enhanced rather than decreased insulin responses when glucose tolerance was the more impaired. Patients in Group B had insulin responses similar to those either of Group A or of Group C. The relationship between the sum of six insulin and six blood glucose values during GTT (sigma IRI and sigma BG) was examined. The sigma BG-sigma IRI plot revealed distinctly different distribution zones for Group A and Group C (Zones A and C). In Group A, sigma IRI values were below 300 microU/ml irrespective of sigma BG values. In Group C, sigma IRI tended to increase, paralleling the increase in sigma BG values in the range of sigma BG values lower than 1400 mg/100 ml. In patients whose sigma BG rose above 1400/100 ml during corticosteroid treatment, the sigma IRI values decreased and entered into Zone A. After the cessation of corticosteroids in a few of these patients, the sigma IRI values recovered and reentered Zone C, concomitant with an improvement in glucose tolerance. Similar recovery of insulin response from Zone A to Zone C was also observed after the treatment of two obese diabetic patients. Thus, patients with glucose intolerance due to extra-pancreatic causes may secrete insulin at a higher rate than normal so long as the FBG level remains below 120 mg/100 ml, but a further deterioration in glucose metabolism may lead to a failure of insulin secretory mechanisms.

Adolescent↗

Insulin binding of erythrocytes in hypoinsulinemic diabetics and its relationship to metabolic states.

We studied the insulin binding of erythrocytes from 26 "well-controlled" (FBG less than 120 mg/dl), and 28 "poorly-controlled" (FBG less than 120 mg/dl) non-obese diabetic patients, and 51 age-matched normal subjects. The capacity of insulin receptors was significantly decreased in well controlled (33.7 +/- 2.2) and poorly controlled (32.4 +/- 2.3) groups compared with normal subjects (43.1 +/- 2.3 sites/cell), while fasting insulin levels of diabetics were comparable to normal subjects but their insulin response to a glucose challenge was considerably decreased. However, the "empty sites" affinity (Ke) was significantly increased in both the well controlled group (5.2 +/- 0.3) and the poorly controlled group (4.8 +/- 0.3) compared with normal subjects (4.0 +/- 0.2 X 10(8) M-1). Thus, the capacity of insulin receptors to bind erythrocytes was decreased but binding affinity was increased in hypoinsulinemic diabetics. The amount of insulin bound in well-controlled diabetics was comparable to that in control subjects at physiological insulin concentrations.

Diabetes Mellitus↗

Effect of a high glucose diet on insulin binding and insulin action in rat adipocytes. A longitudinal study.

To elucidate the mechanisms whereby changes in dietary composition affect the action of insulin on glucose metabolism, insulin binding and glucose uptake and oxidation have been studied in epididymal fat pad adipocytes from rats fed high glucose diets for 5 and 10 days. After 5 days, insulin binding was increased, the mainly to an increased number of receptors (3.4 X 10(5) vs. 2.4 X 10(5) sites per cell) in spite of increased plasma insulin levels (3.0 +/- 0.2 vs. 2.1 +/- 0.1 microgram/l; P < 0.05). The maximal response of glucose oxidation to insulin was increased (925 +/- 55 vs. 510 +/- 58 n moles/2 X 10(5) cells/2h; P < 0.01) and the dose-response curve of glucose uptake was shifted to the left. After 10 days, receptor number decreased to the control level and the effect of insulin on glucose uptake and oxidation (% basal) were similar to controls. Thus, in the early stage of high glucose feeding, insulin receptor number, and insulin sensitivity of glucose uptake, and insulin responsiveness of glucose oxidation were increased.

Adipose Tissue↗

Increase in insulin response after treatment of overt maturity-onset diabetes is independent of the mode of treatment.

The changes in insulin response to a 100 g glucose tolerance test after treatment by diet, sulphonylurea and insulin were compared in non-ketotic diabetic patients who had fasting blood glucose concentrations higher than 160 mg/100 ml. Patients were selected so that their pre-treatment and post-treatment blood glucose levels were comparable between different treatment groups. Their insulin responses were poor initially but increased significantly when the diabetic state was improved by each treatment. The degree of improvement of insulin response was similar between different treatment groups, when their fasting blood glucose decreased below 140 mg/100 ml and the glucose tolerance curves were improved to a similar extent. Pre- and post-treatment sigma IRI values (sum of insulin values during glucose tolerance test, mean +/- SD) were 102 +/- 50 and 200 +/- 37 microU/ml in diet-treated group (n = 28), 90 +/- 40 and 195 +/- 53 microU/ml in sulphonylurea-treated group (n = 48), and 83 +/- 28 and 193 +/- 38 microU/ml in insulin-treated group (n = 13), respectively. The data suggest that the poor insulin response in overt diabetes results not only from an inherent insensitivity of B-cells to glucose but also from the metabolic derangement of diabetes. Poor insulin response and overtly diabetic metabolism seems to form a vicious cycle.

Adult↗

Effects of neuraminidase treatment on solubilized insulin receptor.

Neuraminidase treatment of triton-solubilized insulin receptors from rat fat cell membranes caused release of sialic acid and changed the isoelectric point (pI) of the insulin receptor from 4.7 to 5.6. Neuraminidase had no effect on the number or affinity of insulin receptors. These results indicate that the insulin receptor contains sialic acid, but that this sialic acid is not involved in the binding reaction.

Adipose Tissue↗

Isolation and partial characterization of two immunologically similar vitamin D-binding proteins in rat serum.

Two immunologically similar, probably identical, binding proteins for vitamin D and its metabolites (DBP1 and DBP2) were isolated separately from rat serum after approximately 180-fold purification by novel procedures using Blue Sepharose CL-6B chromatography. The freshly purified DBP1 and DBP2 each showed a single band of protein on polyacrylamide gel electrophoresis, and had alpha-mobility, although DBP1 moved slightly faster than DBP2. DBP1 and DBP2 had the same molecular weight, which was estimated as approximately 54,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric points of DBP1 and DBP2 were estimated as 4.9 and 5.0, respectively, from the results of isoelectric focusing experiments. DBP1 and DBP2 both appeared to have one binding site for 25-hydroxyvitamin D3 per molecule of protein, with apparently similar association constants at 4 degrees C of 5--7 x 10(9) M-1. The amino acid compositions of DBP1 and DBP2 were also determined and compared. A monospecific antiserum against rat DBP2 was prepared in a rabbit and was used for immunological studies of rat DBP. On double immunodiffusion, anti-DBP2 antiserum produced precipitin lines of complete reaction-of-identity against the purified DBP1, the purified DBP2, and rat whole serum. There was no immunological cross-reactivity between rat DBP and sera from man, dog, and rabbit, but mouse serum showed a pattern of partial identity with rat DBP. When rat serum samples were analyzed by immunoelectrophoresis using anti-DBP antiserum, three patterns of precipitin line were observed: a pattern showing the existence of only DBP1, designated as DBP 1-1; a pattern showing the existence of only DBP2, designated as DBP 2-2; and a pattern showing the existence of both DBP1 and DBP2, designated as DBP 2-1. Using single radial immunodiffusion assay for rat serum DBP, the mean (+/- S.D.) serum DBP concentrations were found to be 461 +/- 59 microgram/ml in adult male rats and 328 +/- 16 microgram/ml in adult female rats, and the difference was significant (p < 0.001). In molar terms, DBPs are present in normal rat serum in large excess relative to vitamin D and its metabolites, and most of the serum DBP, therefore, circulates as apo-DBP, not containing a bound molecule of vitamin D or of its metabolites. The immunoprecipitation studies of DBP in rat serum showed that DBPs were common main transport proteins for naturally occurring vitamin D and its metabolites, and that DBP played some, but not a principal, role in the transport of synthetic 1 alpha-hydroxyvitamin D3.

Amino Acids↗

HLA-DRw3 in juvenile onset diabetes mellitus in Chinese.

Thirty-nine juvenile onset diabetes mellitus (JOD) patients and 57 healthy Chinese were HLA-typed in Taiwan. The incidence of HLA-DRw3 was significantly increased in patients when compared with the control group (R.R. = 5.8, P = 0.0027). The frequencies of HLA-B17, which showed linkage disequilibrium with DRw3, and Bw54 were increased in patients, but these increases were not significant because of the small number tested. The DR antigen associated with JOD was the same among Chinese and Caucasians, which suggested that at least one of the susceptibility genes to JOD would be commonly in linkage disequilibrium with DRw3 in the two populations.

Adult↗

Insulin receptor function and insulin effects on glucose metabolism in adipocytes from ventromedial hypothalamus-lesioned rats.

To investigate the mechanism of the development of insulin resistance in hypothalamic obesity, we studied insulin binding, glucose transport, and glucose oxidation in adipocytes from ventromedial hypothalamus (VMH)-lesioned rats 1 and 2 weeks after injury. One week after injury, insulin binding and insulin-stimulated glucose oxidation were increased, but insulin-stimulated glucose transport was similar to control. Two weeks after injury, insulin binding and insulin-stimulated glucose transport were similar to control, but insulin-stimulated glucose oxidation was decreased. Thus, cellular insulin responsiveness was increased in adipocytes from VMH-lesioned rats 1 week after injury; this increase in insulin responsiveness was due mainly to the increased intracellular glucose metabolism. On the other hand, cellular insulin resistance existed in adipocytes from VMH-lesioned rats 2 weeks after injury; this insulin resistance was also due mainly to a defect in intracellular glucose metabolism.

Adipose Tissue↗

Studies of plasma beta-N-acetylglucosaminidase activity in experimental and clinical diabetes mellitus.

Plasma beta-N-acetylglucosaminidase (NAG) activity was measured in streptozotocin diabetic rats, in non-diabetic rats during starvation and refeeding, and in diabetic patients and normal subjects. The enzyme activity increased significantly in the diabetic rats and in the starved non-diabetic rats. The activity decreased markedly after insulin injection in diabetic rats and after refeeding in non-diabetic rats. The plasma NAG activity (532 +/- 24 nmole/hr/ml, M +/- SE) in 21 diabetics with FBS value less than 100 mg/dl was higher than the enzyme activity (455 +/- 15) in 42 normal subjects (p < 0.01), supporting the idea that a more intensive treatment is necessary to normalize the metabolic derangement of diabetes. There was no significant difference between diabetics with and without microangiopathy. While the influence of age and abnormal liver function was noted, there was no correlation between the NAG activity and the platelet adhesiveness or between the NAG activity and the plasma triglyceride. The results suggest that the plasma NAG activity increases in diabetes mellitus, either with microangiopathy or not. The reason for the failure to demonstrate a significant correlation between the total plasma NAG activity and microangiopathy is discussed. The analysis of the subfractionation of the plasma NAG may be necessary to disclose a significant correlation with microangiopathy.

Acetylglucosaminidase↗

Serum 25-hydroxyvitamin D and vitamin D-binding protein levels and mineral metabolism after partial and total gastrectomy.

The effects of gastrectomy, especially total gastrectomy, on the serum levels of 25-hydroxyvitamin D and vitamin D-binding protein and on mineral metabolism were examined. The serum 25-hydroxy-vitamin D levels were markedly decreased in patients with total gastrectomy and Billroth II gastrectomy. Decreased levels of serum vitamin D-binding protein and serum calcium, and increased levels of serum alkaline phosphatase were observed in both patients with partial gastrectomy and patients with total gastrectomy. The results show that vitamin D deficiency could develop in high frequency patients with total gastrectomy and Billroth II gastrectomy, and that deranged mineral metabolism could develop in patients with any type of gastrectomy with or without vitamin D deficiency. The decreased levels of serum vitamin D-binding protein in postgastrectomy patients may be a sensitive reflection of the failure of hepatic protein synthesis.

Aged↗

A selective deficiency of hepatic triacylglycerol lipase in guinea pigs.

The properties of postheparin plasma triacylglycerol-hydrolyzing enzymes were investigated in guinea pig and rat. In rat, lipoprotein lipase and hepatic triacylglycerol lipase were separated on a heparin-Sepharose affinity chromatography. In postheparin plasma of guinea pig, however, hepatic triacylglycerol lipase was almost completely absent, while lipoprotein lipase was present. Hepatic triacylglycerol lipase was also deficient in the liver tissue extract of guinea pig. Plasma lipoprotein compositions of high-fat fed and control guinea pigs were analyzed. One of the outstanding changes found in high-fat fed animals was the presence of chylomicronemia. One guinea pig showed gross hyperlipemia with triacylglycerol concentrations of 2715 mg/100 ml. Plasma triacylglycerol concentrations of each lipoprotein fraction of very low density, intermediate density, low density and high density lipoproteins from high-fat fed animals were almost the same as those of the corresponding lipoprotein fractions from controls. Discussion was focused on the development of chylomicronemia in relation to the defects of triacylglycerol-hydrolyzing enzyme systems in this animal.

Animals↗

Solubilization of insulin binding and degrading activity from guinea pig kidneys.

Insulin binding and degrading activities were solubilized by a nonionic detergent. Triton X-100, from guinea pig kidney particulate fractions (100,000 x g pellet). The solubilized insulin binding activity appeared as a single peak on Sepharose 6B gel filtration with a Stokes radius of 73 A. The pI of the solubilized insulin binding activity determined by flat-bed isoelectric focusing was 5.6. On the other hand, the Stokes radius of the solubilized moelcule with insulin degrading activity was 54 A by the same column with a pI of 5.2. More than 98% of the insulin binding activity could be adsorbed to a column of concanavalin A-agarose, while about 94% of the insulin degrading activity could not be adsorbed to this column. These results strongly suggest that the macromolecule for the insulin binding activity is not identical to that for the insulin degrading activity.

Animals↗