PubMed Health⌕ Search

Biomedical subjects

S Uotani

Publications and source records attributed to S Uotani.

29 records · Page 2Linked to original sources
PubMed1994

Insulin response after treatment depends on fasting plasma glucose level in NIDDM.

We investigated the relationship between the improvement in insulin secretion and glycemic control in non-insulin-dependent diabetes mellitus (NIDDM). Fifty-two patients were classified into three groups according to their pretreatment fasting plasma glucose (FPG) level: Group A, FPG < 7.8 mM, n = 20; Group B, 7.8 mM < or = FPG < 11.1 mM, n = 17; and Group C, 11.1 mM < or = FPG, n = 15. A 75-g oral glucose tolerance test (OGTT) and a glucagon loading test were performed to evaluate insulin secretion before and after treatment. Plasma glucose levels during a 75-g OGTT were decreased significantly after treatment in all groups (P < 0.01). In Group A, there was no significant change in insulin secretion before and after treatment (1466 +/- 213 pM to 1565 +/- 191 pM, P = 0.35). In contrast, in Groups B and C, insulin secretion was poor and suppressed initially, but increased significantly when good glycemic control was obtained after treatment (respectively, 587 +/- 70 pM to 863 +/- 79 pM, P < 0.01, and 621 +/- 94 pM to 1236 +/- 232 pM, P < 0.01). The degree of improvement in insulin secretion in 75-g OGTT correlated positively with the degree of improvement in FPG level after treatment (r = 0.5, P < 0.001). However, the C-peptide response to glucagon did not change before and after treatment. In conclusion, impaired insulin secretion recovered by the good glycemic control in NIDDM with FPG levels above 7.8 mM. Therefore, strict glycemic control (FPG below 7.8 mM) seems important for maintaining good insulin secretion.

Adult↗
PubMed1994

The heterogeneity of whole islet cell cytoplasmic antibodies evidenced by absorption test with glutamic acid decarboxylase.

A recent report identified two islet cell cytoplasmic antibody subclasses using an immunohistochemical method. The islet cell cytoplasmic antibody subclass which reacts with only Beta-cells was termed 'Beta-cell islet cell cytoplasmic antibodies' and another islet cell cytoplasmic antibody subclass which reacts with Beta and non-Beta cells was called 'whole islet cell cytoplasmic antibodies'. The whole islet cell cytoplasmic antibody reactivity with pancreatic islets has been shown not to be abolished by pre-incubation with rat brain homogenate. In this study, we examined the inhibitory effect of purified glutamic acid decarboxylase to islet cell cytoplasmic antibody reactivity among whole islet cell cytoplasmic antibodies and assessed the heterogeneity of islet cell cytoplasmic antibodies. Auto-antibodies to 64,000 Mr islet cell protein (64 K antibodies) were also determined by conventional method. Sera from 17 Type 1 (insulin-dependent) diabetic patients containing whole islet cell cytoplasmic antibodies with more than 20 Juvenile Diabetes Foundation units were used. In 11 (78.6%) of 14 sera positive for 64 K antibodies, the reactivity of islet cell cytoplasmic antibodies was markedly blocked by pre-incubation with purified glutamic acid decarboxylase. In contrast, none of the 64 K antibody-negative sera were blocked. All of the patients showed similar clinical characteristics regardless of the inhibitory effect of glutamic acid decarboxylase on islet cell cytoplasmic antibodies, except for islet cell cytoplasmic antibody titer and glutamic acid decarboxylase antibody titer. The mean log 2 islet cell cytoplasmic antibody titer was 2.4 +/- 0.6 (mean +/- SD) JDF unit in the 'markedly blocked' group and 1.6 +/- 0.3 (mean +/- SD) in the 'never blocked' group. The islet cell cytoplasmic antibody titer was significantly higher (P < 0.05) in the former, and the mean glutamic acid decarboxylase antibody titer was 624 +/- 127.0 (mean +/- SE) units in the 'markedly blocked' group and 127 +/- 55.5 (mean +/- SE) in the 'never blocked' group. The glutamic acid decarboxylase antibody titer was also significantly higher (P < 0.05) in the former. We demonstrated here that some whole islet cell cytoplasmic antibodies are absorbed by purified glutamic acid decarboxylase, suggesting heterogeneity of islet cell cytoplasmic antibodies among the 64 K glutamic acid decarboxylase antibody positive group.

Absorption↗
PubMed1994

Evaluation of islet-specific autoantibodies in Japanese patients with insulin-dependent diabetes mellitus: a comparison between autoantibodies to glutamic acid decarboxylase, autoantibodies to 64 kDa islet cell protein and islet cell antibodies.

Autoantibodies to glutamic acid decarboxylase (GAD), autoantibodies to 64 kDa islet cell protein and islet cell antibodies (ICA) were measured in 79 Japanese patients with insulin-dependent diabetes mellitus (IDDM). The overall prevalences of GAD antibodies, 64K antibodies, and ICA in these patients were 69.6% (55/79), 48.1% (38/79), and 46.8% (37/79), respectively. However, in a subset of these patients with recent onset IDDM (< 1 year) the prevalences of GAD antibodies, 64K antibodies, and ICA were 78.8% (26/33), 66.7% (22/33), and 78.8% (26/33), respectively. Furthermore, the prevalences of GAD antibodies, 64K antibodies, and ICA were significantly decreased in patients with long standing diabetes at 60.9% (28/46), 34.8% (16/46), and 23.9% (11/46), respectively. However, when these patients were divided into two groups by the presence or absence of organ-specific autoimmune disease (OSAD), the mean levels of GAD antibodies and ICA in the patients who gave a positive result were significantly higher in patients with OSAD (397 units and 98 JDF units, respectively) than in patients without OSAD (74 units and 39 JDF units, respectively). These results demonstrate that it is important to evaluate the prevalences and levels of islet-specific autoantibodies when considering disease duration and co-existence of autoimmune disease in patients with IDDM.

Adolescent↗
PubMed1994

Increased insulin responsiveness after CS-045 treatment in diabetes associated with Werner's syndrome.

Werner's syndrome is a rare inheritated disorder characterized by accelerated aging and is often accompanied by diabetes mellitus or impaired glucose tolerance. Previous reports suggest that insulin resistance is involved in the development of diabetes associated with Werner's syndrome. In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. The patients were hospitalized for the duration of the study. During a pretreatment period lasting 8 weeks the patients received a controlled diet, however, their previous treatment was unchanged. Throughout the 4-week treatment period, each subject's blood glucose level was measured 7 times each day (07:30, 10:00, 11:30, 14:00, 17:30, 20:00, 22:00) for 1 week at 8, 4, and 1 week before treatment and at 2 and 4 weeks after treatment. To assess insulin action, the euglycemic glucose clamp technique was performed in these subjects at insulin infusion rates of 20, 120 and 400 mU/kg/min before and after 4 weeks of treatment. After 4 weeks of treatment with CS-045, the mean blood glucose level at each time point measured in this study was markedly lower compared to the corresponding pretreatment level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease.

Autoantibodies to glutamic acid decarboxylase (GAD), previously reported to be the 64,000-M(r) (64K) islet cell protein, were measured by a radioimmunoassay using purified pig brain GAD in 29 insulin-dependent diabetes mellitus (IDDM) patients with autoimmune thyroid disease (AITD) and in 29 sex- and disease duration-matched IDDM patients without AITD. Islet cell antibodies (ICAs) and 64K antibodies were also determined. In IDDM patients with short-duration diabetes (< 1 year), the prevalence and levels of GAD antibodies were 100% (8 of 8) and 609 +/- 166 U (means +/- SE), respectively, in IDDM patients with AITD and 81.8% (9 of 11) and 90 +/- 51 U, respectively, in patients without AITD. In patients with long-standing IDDM (3-22 years), the prevalence and levels of GAD antibodies were 76.2% (16 of 21) and 193 +/- 66 U, respectively, in patients with AITD and 50.0% (9 of 18) and 36 +/- 14 U, respectively, in patients without AITD. For up to 6 years after the onset of IDDM, the levels of GAD antibodies in IDDM patients with AITD were significantly higher than in IDDM patients without AITD. A close and significant correlation was found between GAD antibodies and ICA or 64K antibodies in IDDM patients with AITD. Our results demonstrate that high levels of GAD antibodies were present in IDDM patients with AITD. The observed differences in GAD immunoreactivity between IDDM patients with and without AITD might help evaluate the role of GAD antibodies in IDDM.

Adult↗
PubMed1993

Developmental change of facilitative glucose transporter expression in rat embryonal and fetal intestine.

The developmental expression and localization of facilitative glucose transporter protein (GLUT-1, GLUT-2 and GLUT-5) in rat embryonal and fetal intestine were examined using immunohistochemical methods. The intestines were collected from embryo and fetus (term days, 10 to 20 of gestation), newborn and adult rats (16 weeks after birth). GLUT-1 was expressed abundantly in the gut tube on day 10 of gestation. From day 10 to birth, GLUT-1 was expressed continuously but its expression decreased gradually. In the adult, no GLUT-1 was detected. GLUT-2 was not expressed from day 10 to 14, but began to be expressed in the lumen of the gut tube on day 16, before the intestinal villi were evident. On day 18, when the intestinal villi were developing, GLUT-2 was localized to the basolateral membranes of the enterocytes. A similar pattern of GLUT-2 localization was also observed in newborn and adult rat intestines. The expression kinetics of GLUT-5 were almost the same as those of GLUT-2. GLUT-5 began to be expressed in the lumen of the gut tube on day 16. In contrast to GLUT-2, GLUT-5 was localized to the brush border membranes of intestinal villi after day 18. These results indicate that the expression and localization of each member of the glucose transporter family in the embryonal and fetal intestine vary with the gestational phase. GLUT-1 may be required for glucose metabolism early in gestation, and GLUT-2 and GLUT-5 may be required in both late gestational and perinatal stages.

Animals↗
PubMed1993

Expression of GLUT4 glucose transporter mRNA and protein in skeletal muscle and adipose tissue from rats in late pregnancy.

We investigated the influence of pregnancy on the expression of insulin-regulated glucose transporter (GLUT4) mRNA and protein in skeletal muscle and adipose tissue. GLUT4 mRNA expression in quadriceps muscle from control and pregnant rats was similar in the fasted and fed states. When the level of expression was determined as the immunoreactive GLUT4 content per gram of tissue, the relative GLUT4 protein content of red quadriceps from pregnant rats was significantly higher than that for control rats in both the fed and fasted states. GLUT4 protein expression in white quadriceps from pregnant rats was significantly increased in the fed state compared to control rats, but there was no significant difference in the fasted state. In adipose tissue, the relative GLUT4 protein content was significantly lower in pregnant rats than control rats in the fasted state, but there was no significant decrease in the fed state. Although the expression of GLUT4 protein showed these variations in late pregnancy, there was no significant difference of GLUT4 mRNA expression between control and pregnant rats. These findings suggest that GLUT4 kinetics may differ between late pregnancy and the normal state, and these changes may be related to insulin resistance in pregnancy.

Adipose Tissue↗
PubMed1993

Glucose transporter gene expression in rat conceptus during high glucose culture.

We investigated the expression of glucose transporter genes and protein in embryo and yolk sac during organogenesis and the regulation of glucose transporters during culture in hyperglycaemic media. Erythrocyte-type glucose transporter (GLUT 1) and brain-type glucose transporter (GLUT 3) mRNA were expressed in embryo and yolk sac. The expression of GLUT-1 and GLUT-3 mRNA was abundant on day 9-11 and day 9-10 in the embryo, respectively, and day 9-14 and day 10-11 in the yolk sac, respectively. The levels of GLUT-1 protein in the embryo increased in parallel with the expression of GLUT-1 mRNA during the corresponding period. Immunohistochemical staining of GLUT-1 protein was found principally in the neuroepithelial cells surrounding the neural tube in the embryo on day 10 and appeared in the microvessels surrounding the neural tube after day 12. To test whether the expression of glucose transporter genes and protein was suppressed during hyperglycaemia, conceptuses were cultured in high glucose medium. The abundant expression of GLUT-1 protein was not decreased during culture in high glucose media for 24 h (day 9-10) and was only down-regulated by prolonged exposure to this media for 48 h (day 9-11). We have demonstrated the predominant expression of the high affinity glucose transporter (GLUT 1 and GLUT 3) genes and (GLUT 1) protein in embryo during the early period of organogenesis. The persistently abundant expression of glucose transporter during the critical period of neural tube formation (day 9-10) even in the presence of hyperglycaemia may explain one of the mechanism of increased glucose flux into the neuroepithelium, which may lead to neural tube defects.

Animals↗
PubMed1991

[Study of 123I-IMP SPECT on diabetic patients].

The involvement of peripheral nerves and nerve roots often leads to neurological manifestations which have frequently been described in association with diabetes mellitus. Whether there is any specific involvement of the central nervous system in this process has yet to be determined. Recently, many reports have suggested that significant neurophysiologic abnormalities in the central nervous system can sometimes be found in diabetic patients. In order to accurately examine the existence of central nervous system involvement in patients with diabetes mellitus, comparisons of 123I-IMP (IMP) washout rates were made between normal adults (n = 19, average age 43.3 years) and diabetic patients (n = 23, average age 43.3 years), and these results were graphically demonstrated by color images. Early images were obtained 30 minutes after intravenous injection, while delayed images were made 4 hours after injection. The IMP washout rate was obtained by subtracting the values of the delayed image with the early image. The standard deviation (SD) of the IMP washout rate for each patient was compared to the averaged SD obtained from healthy adults. After calculating the deviation from SD levels of healthy adults, we made an image of the patient's IMP washout rates. These images were divided into seven degrees (I, II: normal, III, IV: borderline, V-VII: abnormal) and the ratio of each degree was expressed by a histogram in each cerebral hemisphere as the washout rate index. In 23 diabetic subjects, seven patients were found to be borderline while sixteen patients were abnormal. These impairments were not related either to the presence of diabetic neuropathies or the duration of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Hepatocyte nuclear factor-1alpha inhibits insulin promoter factor 1-dependent transactivation of the human insulin gene.

To investigate the regulational interaction of hepatocyte nuclear factor-1alpha (HNF-1alpha) and insulin promoter factor 1 (IPF1) on insulin gene expression, either or both of the expression vectors carrying each transcription factor were transiently transfected into HeLa cells, RINm5F cells and MIN6 cells together with the luciferase reporter construct driven by a human preproinsulin gene promoter (-1998 to +237) designated as, pINS-1998/luc. IPF1-transfection into HeLa cells strongly stimulated the luciferase activity to 725 fold that of the basal level. In contrast, HNF-1alpha-transfection resulted in only a 6.7 fold increase. In co-transfection experiments, increasing the amount of HNF-1alpha resulted in an 84.5% and 74.4% decrease in IPF1-stimulated luciferase activity in HeLa and RINm5F cells, respectively. Deletion constructs designated as pINS-248/luc, pINS-213/luc and pINS-185/luc were transfected into RINm5F cells to determine the role of the A3 element and its 5' flanking sequence in the inhibitory effect of HNF-1alpha. The results showed that the inhibiting effects of HNF-1alpha with pINS-213/luc and pINS-185/luc were significantly smaller than those with both pINS-1998/luc and pINS-248/luc. Transfection into MN6 cells with pINS-1998/luc in the absence of IPF1 resulted in constitutional transactivation of the insulin gene, and this transactivation was abolished by the co-transfection with HNF-1alpha. The present data indicate that IPF1 rather than HNF-1alpha predominantly transactivates the insulin gene, and that HNF-1alpha inhibits IPF1-dependent insulin gene transactivation mediated through the 5' flanking sequence of the A3 element. It is suggested that HNF-1alpha may be involved in insulin gene expression as a negative regulator.

Base Sequence↗