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T Awata

Publications and source records attributed to T Awata.

At least 73 records · Page 4Linked to original sources
PubMed1994

A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA.

BACKGROUND: Several families have been described in which a mutation of mitochondrial DNA, the substitution of guanine for adenine (A-->G) at position 3243 of leucine transfer RNA, is associated with diabetes mellitus and deafness. The prevalence, clinical features, and pathophysiology of diabetes with this mutation are largely undefined. METHODS: We studied 55 patients with insulin-dependent diabetes mellitus (IDDM) and a family history of diabetes (group 1), 85 patients with IDDM and no family history of diabetes (group 2), 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and a family history of diabetes (group 3), and 5 patients with diabetes and deafness (group 4) for the mutation. We also studied the prevalence and characteristics of diabetes in 39 patients with a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes who were known to have the mutation and 127 of their relatives (group 5). RESULTS: We identified 16 unrelated patients with diabetes associated with the A-->G mutation: 3 patients from group 1 (6 percent), 2 patients from group 3 (2 percent), 3 patients from group 4 (60 percent), and 8 patients from group 5 (21 percent). We also identified 16 additional subjects who had diabetes and the mutation among 42 relatives of the patients with diabetes and the mutation in groups 1, 2, 3, and 4 and 20 affected subjects among the 127 relatives of the patients in group 5. Diabetes cosegregated with the mutation in a fashion consistent with maternal transmission, was frequently (in 61 percent of cases) associated with sensory hearing loss, and was generally accompanied by impaired insulin secretion. CONCLUSIONS: Diabetes mellitus associated with the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan.

Adolescent↗
PubMed1994

Association of polymorphism in the interferon gamma gene with IDDM.

Cytokines may play important roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon gamma (IFN-gamma) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young-onset (< 10 years) patients (p = 0.0006). The alleles "3" and "6" were increased in the IDDM patients, and a significant increase in the frequency of the "3/6" genotype was observed in the IDDM patient group (9.1%, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6%, RR 3.4, p = 0.004), or in the young-onset patients (16.7%, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4%). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with "3/6" or "6/6" in comparison to the patients with other genotypes. These results suggest that the IFN-gamma gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM.

Adult↗
PubMed1994

Lack of association of the insulin gene region with type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

Although the insulin gene region is implicated in susceptibility to Type 1 (insulin-dependent) diabetes mellitus in Caucasians, significance of this region to Type 1 diabetes in Japanese remains unclear because the class 1 alleles (shorter insertion) of the variable number of tandem repeat in the 5' region of the insulin gene are predominant in both diabetic and non-diabetic subjects. The 5' insulin gene polymorphism was analysed in 75 Japanese patients and 69 control subjects with a precise method using PvuII and a polymorphism specific probe, which enabled us to divide class 1 alleles into four subclasses. Allelic frequencies were not significantly different between Type 1 diabetic patients and control subjects. The polymorphism in the 3' untranslated region of the insulin gene (1127/PstI) was also analysed and found to be tightly linked to the 5' insulin gene polymorphism, and thus was not associated with diabetes. Interaction between HLA-DR and the insulin gene region, which was reported in the French study, was not observed in Japanese. These results suggest that the insulin gene region is not a valuable genetic risk factor for Type 1 diabetes in Japanese.

Age of Onset↗
PubMed1994

Genetic markers for insulin-dependent diabetes mellitus in Japanese.

Although the HLA class II genes are clearly associated with insulin-dependent diabetes mellitus (IDDM) in all ethnic groups, considerable variation in the associated haplotypes is observed among the ethnic groups. In Japanese, DRB1*0405-DQA1*0301-DQB1*0401, DRB1*0901-DQA1*0301-DQB1*0303 and DRB1*0802-DQA1*0301-DQB1*0302 are the major susceptibility haplotypes to IDDM, while DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1502-DQA1*0103-DQB1*0601 are the major resistance haplotypes. The hypothesis that alleles encoding amino acids other than aspartic acid at the DQB1 position 57 contribute to IDDM susceptibility is not applicable to the Japanese, mainly because the first and second susceptibility haplotypes listed above have aspartic acid at DQB1 position 57. In the 5' insulin gene polymorphism, the shorter insertion (class 1 allele) is predominant, and is not associated with diabetes in Japanese. Subdivision of the class 1 alleles also failed to show an association with IDDM in Japanese. The insulin gene region appeared to be of less value as a genetic marker for IDDM in Japanese. Little is known about other genetic markers.

Alleles↗
PubMed1994

Molecular cloning of an equine satellite-type DNA sequence and its chromosomal localization.

We have molecularly cloned portions of equine satellite-type DNA and investigated the organization of the DNA sequence of the cloned segments. Sequence analysis and dot-blot analysis, using the cloned sequence (ES200) as a probe, indicate that the satellite-type DNA sequence consists mainly of 221-bp tandem repeats and represents 3.7-11% of the equine genome. Southern blot analysis further shows that (1) no sequences homologous to ES200 exist in the human, swine, and bovine genomes and that (2) the fragment pattern of the satellite-type DNA produced by ApaI cleavage shows a slight difference among equine DNA samples, indicating a slight sequence variation between individual horses. To localize the satellite-type DNA in the horse genome, chromosome spreads on glass slides were first subjected to G-banding to identify each chromosome and then hybridized in situ with biotin-labeled ES200. The chromosome banding, together with the hybridization, demonstrates that the satellite sequences are preferentially localized on the centromeric regions of all chromosomes except chromosomes 2, 9, and 11.

Animals↗
PubMed1994

A 3-basepair in-frame deletion (delta Leu999) in exon 17 of the insulin receptor gene in a family with insulin resistance.

We studied a woman with acanthosis nigricans and insulin resistance. The patient's Epstein-Barr virus-transformed lymphocytes revealed slightly decreased insulin binding and markedly decreased insulin-stimulated autophosphorylation of the insulin receptor. The nucleotide sequence analysis of the patient's genomic DNA revealed a 3-basepair in-frame deletion in one allele, resulting in the loss of leucine at position 999 of the insulin receptor (delta Leu999). The messenger ribonucleic acid transcripts from the mutant allele in the patient's lymphocytes were not decreased. Insulin-stimulated autophosphorylation of the insulin receptor from cells expressing delta Leu999 mutant insulin receptor complementary DNA was markedly decreased. The proband, her mother, elder brother, and younger brother, who were heterozygous for this mutation, showed moderate or marked hyperinsulinemia during oral glucose tolerance tests. Although fasting glucose levels were normal and fasting insulin values were preserved in all subjects with the mutation for the 8-yr period of observation, a tendency of progressive increase in postload glucose levels was observed. These results suggest that the delta Leu999 mutation, which reduces tyrosine kinase activity, was responsible for insulin resistance and contributed to postload hyperglycemia.

Acanthosis Nigricans↗
PubMed1994

HLA class II alleles in Japanese patients with Graves' disease: weak associations of HLA-DR and -DQ.

To elucidate the associations of the HLA class II alleles with Graves' disease (GD), we examined DRB1, DQA1, DQB1 alleles in 62 Japanese GD patients and 142 control subjects by the PCR-SSOP (polymerase chain reaction-sequence specific oligonucleotide probes) method. We found that DRB1*0803 (P < 0.02), DRB1*1403 (P < 0.03), DQA1*0103 (P < 0.02) alleles and DRB1*0803-DQA1*0103-DQB1*0601 (P < 0.01), DRB1*1403-DQA1*0501-DQB1*0301 (P < 0.02) haplotypes were significantly increased in GD patients. No DQB1 allele revealed a significant association with GD in Japanese. These weak associations may reflect either the heterogeneity of GD in Japanese or the importance of non-HLA factors in the development of the disease.

Alleles↗
PubMed1994

[Non-MHC susceptibility genes in Japanese subjects with insulin-dependent diabetes mellitus (IDDM)].

Genetic factors clearly contribute to the development of autoimmune destruction of pancreatic beta cell in IDDM. The HLA class II genes have an important role in the pathogenesis of Japanese IDDM as they do in Caucasians. Particular HLA class II alleles and haplotypes contribute to the IDDM susceptibility/resistance in Japanese. In the 5' insulin gene polymorphism, the shorter insertion (class 1 allele) is predominant in Japanese, and thus is not associated with IDDM. Subdivision of the class 1 alleles also failed to show an association with Japanese IDDM. The insulin gene region appears not to be a valuable genetic marker for IDDM in Japanese. Recently, we found an association of polymorphism in the IFN-gamma gene with Japanese IDDM.

Asian People↗
PubMed1992

Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR7.8, pc less than 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0, pc less than 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRB1*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.

Alleles↗
PubMed1992

Effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose uptake in mouse pancreatic acini.

In order to examine the effect of islet amyloid polypeptide (IAPP/amylin), a product of the pancreatic beta cell and a major component of islet amyloid deposits, on exocrine pancreatic function, we studied the effect of rat IAPP amide (IAPP-NH2) on 2-deoxy-D-glucose (2-DG) uptake in isolated mouse pancreatic acini. Mouse pancreatic acini were preincubated for 80 min with various concentrations of IAPP-NH2 (1 nM-1 microM) and [3H]2-DG uptake for 20 min was measured. The full effect of IAPP-NH2 on this function was not immediate but increased linearly with time for up to 80 min of incubation. IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini; a detectable effect at 10 nM and a maximal effect at 1 microM. In the presence of 1 microM IAPP-NH2, 2-DG uptake increased by 69 +/- 8% above basal (mean +/- SD, n = 6). The results indicate that IAPP-NH2 stimulates glucose uptake in mouse pancreatic acini, and raise the possibility that IAPP-NH2 plays some physiological role in the insuloacinar axis in mouse pancreas.

Amyloid↗
PubMed1992

Characterization of swine short interspersed repetitive sequences.

Swine genomic DNA segments containing repetitive sequences were isolated from a porcine genomic library using genomic DNA as a probe. Three fragments containing the repetitive sequences from two of the primary phage clones were subcloned for sequence analysis, which revealed six new PRE-1 repetitive families other than those reported earlier by Singer et al. (Nucleic Acids Research 15, 2780, 1987). The frequency of the repetitive sequences in the swine genome was estimated at 2 x 10(6) per diploid genome. Sequence analysis revealed similarities between these repetitive sequences and that of arginine-tRNA gene.

Animals↗
PubMed1991

Additive effect of islet amyloid polypeptide (IAPP/amylin) and insulin on 2-deoxyglucose uptake in mouse pancreatic acini.

The effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose (2-DG) uptake was studied in isolated mouse pancreatic acini in the absence or presence of insulin. Synthetic rat IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini with a half-maximal concentration at 70 nM. The increase in 2-DG uptake by 1 microM IAPP-NH2 or 100 nM insulin was 68% or 60% above basal, respectively. In the presence of both 1 microM IAPP-NH2 and 100 nM insulin, the increase in 2-DG uptake was 145% above basal, indicating that the effects of IAPP-NH2 and insulin on 2-DG uptake were additive. The results suggest that IAPP stimulates glucose uptake in mouse acini probably by a different mechanism from that of insulin.

Amyloid↗
PubMed1991

Uneven-distribution of short interspersed repetitive sequence, PRE-1, on swine chromosomes.

We investigated the distribution of PRE-1 sequences (a swine major SINE) on the swine chromosomes. The investigation demonstrated that PRE-1 sequences are unevenly distributed along the chromosomes as in the case of the human and mouse SINES. The distribution pattern, however, has no simple correlation with Q-band pattern as that of human and mouse SINES. The prominent difference is as follows; PRE-1 is localized on centromeric regions, but human and mouse SINES are not [KORENBERG and RYKOWSKI (1988). Cell, 53: 391-400; BOYLE, BALLARD, and WARD (1990). Proc. Natl. Acad. Sci. U.S.A. 87: 7751-7761].

Animals↗
PubMed1991

Effect of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM.

OBJECTIVE: To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Nineteen NIDDM patients (mean +/- SD age 48.9 +/- 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (greater than 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. RESULTS: The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA1c decreased (n = 19, FPG, 11.0 +/- 2.4 vs. 8.4 +/- 2.7 mM [before vs. after], P less than 0.001; HbA1c, 8.0 +/- 1.1 vs. 7.4 +/- 1.3%, P less than 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 +/- 49.8 vs. 56.5 +/- 24.6 pM [before vs. after], P less than 0.05; area under the curve of IRI, 540.3 +/- 350.5 vs. 426.4 +/- 216.3 pM.h, P less than 0.05). CONCLUSIONS: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.

Blood Glucose↗
PubMed1990

Hypervariable region 5'-flanking [Leu A3]insulin gene of insulin Tochigi is different from those of insulin Wakayama I,II.

Three families with abnormal insulinemia have been reported in Japan and sequencing analysis revealed that they had the same point mutation in one allele of the insulin genes causing [Leu A3]insulin. To estimate whether or not this same mutation came from a common ancestor we determined the sequence of the hypervariable region 5'-flanking the third [Leu A3]insulin allele (insulin Tochigi). This region is composed of 42 tandem repeating oligonucleotides, is 599 base pairs long and the sequence is 5' cdi jfa faa aba baa aaa fab aaa caa aac aca cba aaf ccb 3' (abbreviated as a = ACAGGGGTGTGGGG; b = ACAGGGGTCTGGGG; c = ACAGGGGTCCTGGGG; d = ACAGGGGTCCGGGG; f = ACAGGGGTCCCGGGG; i = ACAGGGTCCTGGGG; j = ACAGGGGTGTGAGG). The length of this region is different from those of the first and second [Leu A3]insulin alleles (insulin Wakayama I,II). This difference suggests either that insulin Tochigi and insulin Wakayama I,II are not of the same origin, or that three cases of [Leu A3]insulin in Japan have the same ancestor but recombination has occurred in this region at some point in the past.

Base Sequence↗
PubMed1990

High frequency of aspartic acid at position 57 of HLA-DQ beta-chain in Japanese IDDM patients and nondiabetic subjects.

The HLA-DQ beta-chain (DQB1) genes of 72 Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 85 control subjects were studied with polymerase chain-reaction (PCR) amplification and allele-specific oligonucleotide hybridization. DQW4 (DQBBlank) and DQw9 (DQB3.3) were increased in IDDM patients compared with the control subjects, and DQB1.2, DQB1.9, and DQw7 (DQB3.1) were decreased. Thirty-five (48.6%) IDDM patients had both alleles carrying an aspartic acid at position 57 of the DQ beta-chain (Asp 57), 35 (48.6%) were Asp 57/non-Asp 57 heterozygous, and 2 (2.8%) had non-Asp 57 alleles only. Of 85 control subjects, the respective values for these three genotypes were 49 (57.6%), 29 (34.1%), and 7 (8.2%), respectively. The high frequency of Asp 57 alleles in both IDDM and control subjects contrasts with data for Whites. Therefore, the Asp 57 hypothesis that the presence of an aspartic acid at position 57 of DQ beta-chain provides protection against developing IDDM is not tenable for Japanese IDDM patients. The DRB1 gene, particularly position 57 of the DR beta-chain, may contribute to IDDM susceptibility in Japanese.

Adolescent↗