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Biomedical subjects

A Sekikawa

Publications and source records attributed to A Sekikawa.

54 records · Page 3Linked to original sources
PubMed1996

Human arterial smooth muscle cell proliferation in diabetes.

In the present study, we focus on the proliferation of human arterial smooth muscle cells (SMCs) from NIDDM patients (DM-SMCs) to clarify the reactivity to the growth factor(s) in fetal calf serum (FCS) and the factor(s) secreted by T-cells. The proliferation of DM-SMCs was significantly greater than SMCs from nondiabetic patients (nonDM-SMC). DM-SMC conditioned medium (DM-condMed) increased the growth of nonDM-SMCs. These results suggest that the growth factor is secreted from DM-SMCs as an autocrine system, which increases the proliferation of nonDM-SMCs. T-cells increased DNA synthesis of SMCs, and DM-SMCs strikingly reacted to T-cells. The present results support a function of T-cells in stimulating SMC growth. In conclusion, human arterial SMC proliferation is increased in diabetes in the same fashion as in experimentally induced diabetes in animals through responses to growth factors and an increased autocrine system. These results provide a mechanism for the increase in atherosclerotic disease in diabetes.

Adult↗
PubMed1995

Determination of the NMR solution structure of a specific DNA complex of the Myb DNA-binding domain.

The solution structure of a specific DNA complex of the minimum DNA-binding domain of the mouse c-Myb protein was determined by distance geometry calculations using a set of 1732 nuclear Overhauser enhancement (NOE) distance restraints. In order to determine the complex structure independent of the initial guess, we have developed two different procedures for the docking calculation using simulated annealing in four-dimensional space (4D-SA). One is a multiple-step procedure, where the protein and the DNA were first constructed independently by 4D-SA using only the individual intramolecular NOE distance restraints. Here, the initial structure of the protein was a random coil and that of the DNA was a typical B-form duplex. Then, as the starting structure for the next docking procedure, the converged protein and DNA structures were placed in random molecular orientations, separated by 50 A. The two molecules were docked by 4D-SA utilizing all the restraints, including the additional 66 intermolecular distance restraints. The second procedure comprised a single step, in which a random-cell protein and a typical B-form DNA duplex were first placed 70 A from each other. Then, using all the intramolecular and intermolecular NOE distance restraints, the complex structure was constructed by 4D-SA. Both procedures yielded the converged complex structures with similar quality and structural divergence, but the multiple-step procedure has much better convergence power than the single-step procedure. A model study of the two procedures was performed to confirm the structural quality, depending upon the number of intermolecular distance restraints, using the X-ray structure of the engrailed homeodomain-DNA complex.

Animals↗
PubMed1995

Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotocin-induced diabetic rats.

Although there is no concept of insulin resistance in traditional Kampo (Chinese) medicine and Indian medicine, we had the hypothesis that some drug in a mixture of crude drugs which was believed to ameliorate diabetes mellitus may have had the effect of improving insulin resistance. To test this hypothesis, the effects of Seishin-renshi-in (Chinese medicine) and Gymnema sylvestre (Indian medicine) on the insulin resistance of streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Oral administration of Seishin-renshi-in (800 mg/kg/day) with injections of a minimum dose of Ultralente insulin decreased urine volume and urinary glucose excretion during a 7-day treatment period and improved the insulin stimulated glucose uptake in peripheral tissues, as well as improving the insulin suppressed hepatic glucose output during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did not improve insulin resistance. We conclude that Seishin-renshi-in, with a small dose of insulin, improved insulin resistance in streptozotocin-induced diabetic rats, but Gymnema sylvestre did not.

Animals↗
PubMed1995

Insulin-like growth factor I resistance in peripheral tissue but not in liver in streptozotocin-induced diabetic rats.

The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rats and streptozotocin-induced diabetic rats, a model of insulin-dependent diabetes mellitus (IDDM), and compared with that of insulin. Glucose uptake by peripheral tissues was stimulated by intravenous administration of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose dependent manner, with a potency of 1/52 that of insulin estimated on the basis of the ED50 molar ratio in normal rats. In streptozotocin-induced diabetic rats, the maximum effects of IGF-I and insulin were reduced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose output in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis of the ED50 values. In streptozotocin-induced diabetic rats, a dose-response curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insulin resistance, but a leftward shifting of the suppressive effect of IGF-I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was rather increased in streptozotocin-induced diabetic rats, in contrast to the resistance of both peripheral tissues and liver to insulin.

Animals↗
PubMed1994

Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices.

The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3). We have determined the solution structure of a specific DNA complex of the minimum DNA-binding domain (R2R3) by heteronuclear multidimensional NMR. Both R2 and R3 contain three helices, and the third helix in each is found to be a recognition helix. R2 and R3 are closely packed in the major groove, so that the two recognition helices contact each other directly to bind to the specific base sequence, AACNG cooperatively; this is a significant arrangement of recognition helices. The three key base pairs in this sequence are specifically recognized by Asn-183 (R3), Lys-182 (R3), and Lys-128 (R2). In contrast, R1 has no specific interactions with DNA from our NMR study of the DNA complex of the full DNA-binding domain (R1R2R3).

Amino Acid Sequence↗
PubMed1993

Thiazolidinediones (AD-4833 and CS-045) improve hepatic insulin resistance in streptozotocin-induced diabetic rats.

To investigate whether thiazolidinediones (AD-4833 and CS-045), new oral antidiabetic agents, are effective in insulin-dependent diabetes mellitus, the effect of thiazolidinediones on streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Diabetic rats were divided into five groups: (1) intensively insulin treated group given a daily injection of 4-6 units Ultralente insulin, (2) AD-4833 group treated with a daily injection of 2 units Ultralente insulin, the minimal dose to make urinary ketones negative, and ingestion of 10 mg/kg of AD-4833 suspended in 5% gum arabic, (3) gum arabic group treated in the same way as the AD-4833 group except for the active drug, (4) CS-045 group treated with the same insulin injection and ingestion of 200 mg/kg CS-045 suspended in 0.5% chlormethyl cellulose, (5) chlormethyl cellulose group treated as the control for the CS-045 group. Seven days after these treatments, all five groups of diabetic rats and normal control rats were subjected to the glucose clamp study in which 3 mU.kg-1.min-1 porcine insulin was continuously infused. Glucose infusion rates (GIR) for the gum arabic and chlormethyl cellulose groups were significantly lower than in control rats, and the rates of hepatic glucose output (HGO) of these two groups were not suppressed, indicating the presence of hepatic insulin resistance. Intensive insulin treatment as well as administration of AD-4833 and CS-045 with a minimal dose of insulin restored both GIR and HGO towards normal levels. It is concluded that thiazolidinediones improved hepatic insulin resistance in the presence of a minimal dose of insulin.

Animals↗
PubMed1993

Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan.

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in the Funagata area of Japan. RESEARCH DESIGN AND METHODS: The total eligible subjects was 1163, all were > or = 45 yr of age, and 52 were known diabetic patients. Data collected included body height, weight, and answers to medical questionnaires. A 75-g OGTT was done in the morning. WHO criteria were used to classify the current diabetes status of study participants. RESULTS: Of the 1111 scheduled for the OGTT, 868 took the test; the participation rate was 77.8%. The prevalence of diabetes was 10.5 and 12.9%, and the prevalence of IGT was 14.7 and 18.0% for men and women, respectively. The prevalence of undiagnosed diabetes (4.9%) was almost equal to that of previously diagnosed diabetes (4.5%). CONCLUSIONS: The prevalence of diabetes in the Funagata area was two to four times higher than that of previous reports in Japan, in which many investigators used a urinary glucose test as a preliminary test. This difference is attributed to the method of determining the prevalence of diabetes.

Age Factors↗
PubMed1993

[Do blood glucose levels in the elderly have different metabolic significance than in non-elderly subjects?].

Diagnostic criteria of diabetes mellitus in elderly people are still controversial. The major questions are whether (1) effects of hyperglycemia in generating diabetic complications are the same as in younger diabetics, (2) too many diabetics might be diagnosed in the elderly by the criteria proposed by WHO and Japan Diabetes Society. To answer these questions, we carried out two studies. Blood glucose data were collected from population-based studies and from voluntary health check-up studies. Fasting blood glucose values were classified by sex and the age (-49, 50-64, 65-years old). Population-based studies showed no age-dependent change in blood glucose. However, data from health check-up studies showed an increase in median values from the group aged 50-64 and the 65 and older group. Two-hour values after glucose tolerance tests were classified by age and the fasting blood glucose (-99, 100-119, 120-139, and 140- mg/dl). The eldest and 140- mg/dl group showed the highest 2-hour values. Effects of hyperglycemia on the appearance of diabetic complications were studied in patients being follow-up in three diabetes clinics. Patients who has a history of one year or less and without any retinopathy on the first visit to the clinic were registered. Data were analyzed by the Kaplan-Meier method and the appearance of retinopathy was used as the end point. There were no difference in the rate of appearance of retinopathy between the age groups (-49, 50-64 and 65-years old). No age effect on the hyperglycemia-dependent appearance of retinopathy could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Solution structures of Myb DNA-binding domain and its complex with DNA.

The DNA-binding domain of Myb consists of three imperfect tandem repeats, each of which contains three conserved tryptophans. The solution structure of the third repeat was established by NMR; it includes three helices maintained by a hydrophobic core formed by three tryptophans, together with two histidines, and the second and third helices form a helix-turn-helix-related motif. Here, we report the whole structure of the DNA-binding domain, as determined by NMR. Each of the first and second repeats resembles the third one in structure, retaining three helices. As a whole, the DNA-binding domain contains an entirely unique structure, a triple helix-turn-helix-related motif. To determine the role of each repeat in DNA-binding, a 16-mer DNA duplex that is specifically recognized by Myb was synthesized and then its complex with the DNA-binding domain has been investigated by 3D-NMR. The interaction mode between the whole DNA-binding domain and the duplex has shown that the third helix in each repeat likely locates in the majour groove of DNA. It is suggested that the Myb DNA-binding domain wraps around the DNA duplex by fitting the triply repeated helix-turn-helix-related motifs in the majour groove.

Base Sequence↗
PubMed1992

Insulin antibody does not cause insulin resistance during glucose clamping in rats.

Although it has often been stated that insulin antibodies cause insulin resistance, this concept is still controversial. The effect of insulin antibody GP30, commonly used in insulin radioimmunoassay, on insulin action was investigated in Wistar rats in vivo by the euglycemic glucose clamp technique. As a preliminary experiment, the equilibrium time required for insulin antibody to bind with endogenous insulin was examined. One hundred microliters/kg insulin antibody took 60 min or more to attain equilibrium, but 10 microliters/kg insulin antibody almost immediately equilibrated with endogenous insulin. During a 60-min glucose clamp study, 2 mU/kg/min porcine insulin was infused with 100 microliters/kg insulin antibody. At steady state, during the last 20-min period, the mean glucose infusion rate was 2.10 +/- 0.85 mg/kg/min (n = 5, mean +/- SD), significantly lower than the 5.77 +/- 1.61 mg/kg/min of the control, indicating insulin resistance before equilibrium was reached. However, the glucose infusion rates during the clamp with 10 microliters/kg insulin antibody and 100 microliters/kg insulin antibody infused 75 min before the insulin were 6.10 +/- 1.44 and 7.12 +/- 1.19 mg/kg/min, respectively, no different from the control. In these instances, free insulin levels measured by radioimmunoassay using the polyethyleneglycol method were 43.8 +/- 20.4 and 15.4 +/- 6.1 microU/ml, respectively, lower than the control (77.0 +/- 16.1 microM/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease.

We attempted to analyze the association of hyperthyroid Graves' disease with non-insulin-dependent diabetes mellitus (NIDDM). Forty-nine patients (23 males and 26 females; 7.6%) of a total of 647 patients with hyperthyroid Graves' disease had NIDDM, several years before or after Graves' disease was diagnosed. Only 1 patient had insulin-dependent diabetes mellitus. Compared with the general Japanese population (n = 9,133), the incidence of NIDDM (n = 348; 3.9%) in patients with Graves' disease was higher in all age groups. Only 4 patients (8.2%) of the 49 hyperthyroid patients with NIDDM had a history of being overweight (body mass index > 25). In contrast, 276 (79.9%) of the 348 diabetic patients were currently or previously overweight. Moreover, the incidence of a family history of diabetes (13 of the 49 hyperthyroid Graves' patients with NIDDM; 26.5%) was also lower in the patients with NIDDM in the general Japanese population (50% incidence). The male:female ration in patients with Graves' disease and NIDDM was 1:1.1; much different from that in the total Graves' disease population (1:4.1). Analysis of the HLA loci A, B, C, DR and DQ (35 determinations) in 35 hyperthyroid patients with NIDDM and in 386 subjects from the general population revealed a highly significant difference between them in the incidence of HLA-Cw4, -DR2, -DQw1, -DQw3 and -DQw4. This study suggests that there was an association of Graves' disease with NIDDM. A significant association of HLA-DR and -DQ loci was observed in hyperthyroid Graves' patients with NIDDM.

Adolescent↗
PubMed1991

Hyperglycaemia but not hyperinsulinaemia prevents the secretion of glucagon-like peptide-1 (7-36 amide) stimulated by fat ingestion.

The effect of insulin and glucose on fat-induced gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1 (7-36 amide)) was studied in five healthy subjects during continuous glucose infusion (Protocol 1) and during hyperinsulinaemic euglycaemic blood glucose clamp (Protocol 2). In Protocol 1, 50 g fat was orally ingested and glucose was infused at a rate of 0.7 g/kg/h for 2 h continuously from the time of fat ingestion. Either glucose infusion alone or fat ingestion alone was carried out in the same subjects as the control. The release of GIP and GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state. In protocol 2, 50 g of fat was ingested and insulin was infused at a rate of 0.1 U/kg/h with an artificial pancreas system to obtain the normoglycaemic hyperinsulinaemic state. The release of GIP was significantly suppressed in the normoglycaemic hyperinsulinaemic state as well as in the hyperglycaemic hyperinsulinaemic state. However, the release of GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state but not in the euglycaemic hyperinsulinaemic state. Thus, it is concluded that insulin inhibits fat-induced GIP, but not GLP-1 (7-36 amide), secretion and that glucose is likely to inhibit GLP-1 (7-36 amide) secretion.

Adult↗
PubMed1990

Is examination of fructosamine levels valuable as a diagnostic test for diabetes mellitus?

In order to develop a simple, one-point diagnostic test for diabetes mellitus in a mass population surveys, we measured levels of fructosamine (FRA), one of the glycated proteins. Seven hundred and thirty-eight people had their levels of fasting plasma glucose (FPG), FRA and hemoglobin A1c (HbA1c) examined before taking 75 g oral glucose tolerance tests (OGTT). The results of OGTT distinguished a diabetic group (DM) of 143 from a non-diabetic group (non-DM) of 595 subjects. Since there was a significant correlation between FRA levels and plasma glucose levels 2 h after OGTT (PG-2h), as well as between FPG and PG-2h, a discriminant analysis using FPG and FRA was carried out in order to separate the DM group from the non-DM group. According to this analysis, a positive f, where f = FPG-(mg/dl) + 12.0 FRA(mmol/l) - 150, would determine a subject to be a diabetic. However, the sensitivity of this analysis was only 0.521. It can be concluded that the sensitivity of a simple, one-point determination for diabetes mellitus using measured levels of FRA was insufficient, even by application of discriminant analysis, and that the OGTT is still needed for a diagnostic test for diabetes mellitus in mass population surveys.

Biomarkers↗
PubMed1989

Insulin resistance in septic rats--a study by the euglycemic clamp technique.

Male Wistar rats weighing 250 +/- 30g were made septic by cecum ligation and perforation. Peripheral and hepatic sensitivity to insulin was assessed by the euglycemic glucose clamp technique with simultaneous [3H]glucose infusion. Hepatic glucose output was not suppressed by the insulin infusion in the septic rats in contrast with the controls. Glucose utilization by the peripheral tissues was not significantly different between the septic and control rats. Counterregulatory hormone levels were higher in the septic group. Our data suggest that the liver is the site of insulin resistance in the septic state.

Animals↗
PubMedDate not supplied

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in a rural area of Japan. The Funagata diabetes study.

PURPOSE: To determine the prevalence of type 2 diabetes and impaired sucrose tolerance (IGT) among people aged 40 and over in a rural area, Funagata, Japan, by using a 75-g oral glucose tolerance test (OGTT), and to compare the prevalence to that obtained from a more urban area, Hisayama, Japan. METHODS AND RESULTS: Total eligible subjects for the Funagata study were 3526. Among them, 140 were confirmed to have diabetes judged by the 1985 WHO criteria. A 75-g OGTT was conducted, excluding the 140 known cases of diabetes. The 1985 WHO criteria were used to classify the current diabetes status of participants. The overall participation rate was 74.4%. The prevalence of diabetes (known and newly diagnosed cases combined) was 9.1% for men and 10.8% for women. The prevalence of IGT was 12. 0% for men and 16.5% for women. Age-adjusted prevalence (using 1990 Japanese census) of diabetes and IGT in men in Hisayama is two times higher than in Funagata (12.8% vs. 6.8% for diabetes, 19.5% vs. 10. 3% for IGT). Age-adjusted prevalence of IGT in women in Hisayama is significantly higher than in Funagata. CONCLUSIONS: The prevalence of type 2 diabetes among people aged 40 and over is approximately 10% even in a rural area of Japan. Prevalence of diabetes and IGT is much higher in an urban area than in a rural area in Japan.

Adult↗
PubMedDate not supplied

Telepreventive medicine.

There have been dramatic improvements in health during the past 50 years, and public health measures have made a major contribution. Much of public health consists of information transfer. The application of telecommunications technology to public health and preventive medicine would enhance our ability to transmit information and improve global health. The idea of telemedicine has received considerable attention but has not thus far included preventive medicine. We have outlined a global electronic health network with seven main components: connectivity, telemonitoring of disease, "distance education" for public health workers, electronic connection of nongovernment organizations, a combined degree in public health and communications, an electronic scientific research server, and a home page on the World Wide Web. A commitment to the integration of telecommunications and public health holds great promise for improving the health status of the world's population.

Computer Communication Networks↗