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Biomedical subjects

K Komeda

Publications and source records attributed to K Komeda.

At least 37 records · Page 2Linked to original sources
PubMed1997

Change of plasma 1,5-anhydro-D-glucitol levels after the onset of diabetes in spontaneous diabetes prone BB/Wor/(/)Tky rats.

Plasma 1,5-anhydro-D-glucitol (AG) is a marker of the diabetic state and also reflects the glycosuria induced by hyperglycemia but not by renal pathology. To investigate the benefits of the AG determination in order to diagnose diabetes in BB/Wor/(/)Tky rats, AG was measured in non-diabetic (n = 104) and diabetic (n = 113) BB/Wor/(/)Tky rats. AG was significantly higher in non-diabetic rats than in diabetic rats (25.2 +/- 9.3 vs 4.1 +/- 7.4 micrograms/ ml, mean +/- SD, p < 0.001). The best cut-off level for AG (8.5 micrograms/ml) was highly specific (100%) for ruling out diabetes and fairly sensitive (82.3%) to detect diabetes. Based on the AG cut-off levels, 90% of false-negative diabetic rats (18/20) were observed within 4 days after the onset of diabetes, which corresponded to 38.3% in diabetic rats (18/47) at that time. The false-negative diabetic rats and positive rats could be effectively distinguished based on the cumulative points given according to the urinary glucose after the onset of diabetes. 1 point for each cross [+] indicating glycosuria using the Testape, i.e. 2 or less points false negative and 4 or more points for diabetic rats in the first 4 days. In conclusion, there is a close inverse relation between the level of plasma AG and the amount of glycosuria detected just after the onset of overt diabetes in BB/Wor/(/)Tky rats.

Animals↗
PubMed1997

Induction of cell killing, mutation and umu gene expression by 6-mercaptopurine or 2-thiouracil with UVA irradiation.

When Escherichia coli cells were irradiated by UVA in the presence of 6-mercaptopurine (6-MP) or 2-thiouracil (S2Ura), two kinds of repair-deficient strains of recA- and uvrA- were killed more efficiently than the parental wild-type strain having normal repair capacities. In addition, these agents with UVA exposure greatly induced the incidence of mutations in the uvrA- strain as compared with the wild-type strain but not the recA- strain. Furthermore, the induction of expression of umuDC genes was investigated in two Salmonella typhimurium strains, TA1535 and TA1538, carrying a pSK1002 plasmid. In these systems, it is easy to measure beta-galactosidase activities for the induced activities of SOS responses. These agents with UVA exposure also induced expression of the umuDC genes. These results suggest that 6-MP and S2Ura with UVA induce DNA damage which is repairable by the excision repair mechanism.

Adenosine Triphosphatases↗
PubMed1994

Reciprocal changes in left ventricular collagen alpha 1 chain gene expression between types I and IV in spontaneously diabetic rats.

The characteristic features of diabetic cardiomyopathy have been reported to be increased collagen formation associated with impairment of ventricular performance, based on experimental models of diabetes. The present study was therefore designed to clarify collagen gene expression in hearts obtained from female spontaneously diabetic BioBreeding Worcester Tokyo (BB/W@Tky) rats. Cardiac hypertrophy was observed as early as 14 weeks in diabetic BB/W@Tky rats, i.e. 4 weeks after the onset of diabetes. Left ventricular gene expression of collagen alpha 1 (I) was decreased to 10.6% of the control level. In 24-week-old diabetic rats, which had more marked cardiac hypertrophy, the level of alpha 1 Type I collagen mRNA was further decreased to 5.7% of the control level, whereas collagen alpha 1 (IV) mRNA demonstrated a 3-fold increase. As a result, a ratio of collagen alpha 1 (IV) to actin mRNA was positively correlated with plasma glucose concentration. These results suggest that hyperglycemia may alter the gene expression of extracellular matrix proteins, resulting in the morphological and functional changes seen in diabetic cardiomyopathy.

Actins↗
PubMed1993

Apolipoprotein E metabolism in sciatic nerves of diabetic rats. Implication for diabetic neuropathy.

Apolipoprotein (apo) E secreted by macrophages plays an important role in nerve injury and repair. We investigated the disturbance of neural apo E metabolism in diabetic rats and its relation to diabetic neuropathy. In BB/W rats, genetically diabetes prone rats, the secretion of apo E from sciatic nerves was 3-fold greater than that in control rats. Furthermore, a similar enhancement of apo E secretion was observed in injured nerves of STZ-induced diabetic rats (2-fold) as compared with those of nondiabetic rats, and this was reversible with insulin treatment. Histological examination of the nerves revealed more extensive infiltration of mononuclear cells in the injured nerves of STZ-induced diabetic rats than in those of non-diabetic rats. This is consistent with the findings that chemotactic activities for mononuclear cells, which were released from injured nerves, were greater in the STZ-induced diabetic rats than in the non-diabetic rats. From these results we conclude that the recruitment of monocyte/macrophages into injured nerves is enhanced in diabetes, thereby causing derangement of neural apo E metabolism. These abnormalities might contribute to the development of diabetic neuropathy.

Adult↗
PubMed1991

An ultrastructural study on the pancreatic islet B cells in diabetic herbivorous voles.

An ultrastructural study was performed on the pancreatic islet cells of normal herbivorous voles and of voles in which diet-induced diabetes had been induced by feeding a low-fibre, high-concentrate diet. Examination of the pancreatic islet cells revealed degranulation and a well-developed Golgi apparatus and rough endoplasmic reticulum in the B cells of the slightly diabetic voles showing moderate hyperglycaemia and hyperinsulinaemia, and markedly degenerative B cells with almost complete absence of secretory granules in the severely diabetic voles showing marked hyperglycaemia and hypoinsulinaemia. These results indicate that the pancreatic B cells had become hyperfunctional so that insulin secretion was increased in the slightly diabetic voles; thereafter the B cells degenerated rapidly and the voles fell into insulin deficiency.

Animals↗
PubMed1991

Effect of cholera toxin on serum levels of thyrotropin and thyroid autoantibodies in biobreeding/Tokyo (BB/TKY) rats.

The effect of cholera toxin (CT) on the thyroid-pituitary axis and the immune system was examined in Bio-Breeding/Tokyo (BB/TKY) rats, which spontaneously develop insulin-dependent diabetes mellitus (DM) and lymphocytic thyroiditis (LT). Intravenous administration of CT (5 micrograms/100 g body weight) every other week starting at 6 weeks of age resulted in a significant decrease in the serum thyrotropin (TSH) level at 12 and 14 weeks of age when compared with saline treated littermates. CT stimulated rat thyroid cells to proliferate in vitro. Furthermore, serum anti-thyroglobulin antibody (ATA) titers were also significantly decreased in 14-week-old rats treated with CT. In vitro ATA production by spleen cells from BB/TKY rats was inhibited by CT. Antibodies to thyroxine were detected in both CT-treated and control rats. It is of interest that the ratio of W3/25+ helper/inducer cells to OX8+ suppressor/cytotoxic cells was significantly decreased in CT-treated rats. However, there was no significant difference in the incidence of DM and LT between the two groups of rats. The present study showed that CT suppressed ATA production both in vivo and in vitro, and had a stimulatory effect on thyrocytes in BB/TKY rats.

Animals↗
PubMed1991

Effects of PGE1 on the development of diabetes and surface markers of lymphocytes in BB/W/Tky rats.

To study the effect of an oral prostaglandin E1 (PGE1) derivative and/or lipo PGE1 on the onset of diabetes, these agents were administered to Bio-Breeding/Worcester/Tokyo (BB/W/Tky) rats from 4 to 13 weeks of age. Lymphocyte subsets in peripheral blood from normal Wistar and BB/W/Tky rats were measured before and for one week after administration of PGE1 using laser flow cytometry. Results showed that 14/16 (87.5%) of the BB/W/Tky rats administered PGE1 developed diabetes vs. 6/12 (50%) in the control BB/W/Tky rats. In normal Wistar rats, PGE1 significantly increased the W3/25+OX39+ and OX8+OX39+ cells. In BB/W/Tky rats, PGE1 significantly increased the OX19+OX6+, OX19+OX39+, W3/25+OX6+, W3/25+OX39+, OX8+, OX8+OX6+, OX8+OX39+ and OX39+ cells, while decreasing the OX6+ cells. We conclude that the administration of PGE1 to BB/W/Tky rats accelerates the development of spontaneous diabetes and alters the surface markers of lymphocytes.

Aging↗
PubMed1990

Hyperreninemia due to increased renal renin synthesis in BioBreeding Worcester rats.

It is well known that diabetes mellitus is often associated with hypertension. We previously reported the unresponsiveness of renin release to volume depletion with impaired renal prostaglandin E2 synthesis in rats with streptozotocin-induced diabetes. However, we have found that BioBreeding Worcester rats, spontaneously susceptible to diabetes mellitus either before or after the onset of diabetes, showed a pronounced fourfold to ninefold increase in plasma renin activity in comparison with control Wistar rats. Furthermore, these rats developed mild hypertension as high as 134 mm Hg after the age of 90 days. The hyperreninemia responded to 1-week sodium loading or restriction; the blood pressure increased during sodium loading. Oral administration of captopril (30 mg/kg) for 1 week resulted in a large blood pressure decrease (-47.1 +/- 5.9 mm Hg, n = 10) in comparison with controls (-17.0 +/- 4.7 mm Hg, n = 12). Vascular response to angiotensin II was also attenuated. Plasma angiotensin II levels were 5.7-fold higher and associated with a 1.5-fold increase of plasma aldosterone concentration compared with control rats, whereas angiotensinogen-plasma concentrations were lower than in control rats. The renal renin content determined enzymatically or histochemically was more enhanced in BioBreeding Worcester rats than in control rats, but the renal renin messenger RNA levels did not differ. These results suggest that the strain-specific hyperreninemia in BioBreeding Worcester rats might be due to posttranscriptional abnormalities of renal renin synthesis. Further work is needed to elucidate the specific mechanism or mechanisms responsible.

Angiotensin II↗
PubMed1990

MHC class II molecules (Ia-antigens) on macrophages in BB/W rats.

The percentage, absolute number and expression of Ia-antigen of macrophages (Mø) in peripheral blood cells (PBC) and splenocytes from Bio-Breeding/Worcester (BB/W) rats were evaluated. The percentage of Mø in PBC and splenocytes from BB/W rats was significantly higher than those in normal Wistar rats from Clea Japan Inc. (NW/C) and Charles River Japan Inc. (NW/CR). The percentage of Ia-positive Mø in PBC and splenocytes from BB/W rats was significantly increased compared with that in NW/C rats. On the other hand, there was no significant difference in the percentage of Ia-positive Mø of PBC between BB/W and NW/CR rats, and the percentage of Ia-positive Mø in the spleen from BB/W rats was significantly lower than those in NW/CR rats. Thus, the quantity of MHC class II molecules on circulating Mø is not related to the pathogenesis of diabetes mellitus in BB/W rats.

Animals↗
PubMed1989

Detection of nuclear protein antigens to antinuclear antibodies in serum of NOD mouse.

Nuclear protein antigens to the antinuclear antibodies in serum of non-obese diabetic (NOD) mice were investigated. In the serum of diabetic NOD female mice (20 weeks old), the antinuclear antibodies were detected by indirect immunofluorescence assay using frozen sections of liver of C 57 BL/6 J or NOD mice as antigen. Nuclei were separated from the liver of C 57 BL/6 J mice and solubilized. Solubilized nuclear antigens were analyzed by SDS PAGE-Western immunoblotting techniques. Nuclear protein antigens with molecular weights of 26,000, 32,000 and 65,000 showed strongly positive reactions with the antinuclear antibodies in the serum of the NOD mouse.

Animals↗
PubMed1989

Creeping: a new mutant rat with neurological disease.

We describe a new mutant rat, named creeping, that exhibits severe ataxia characterized by a creeping posture due to the inability to stand up. Affected animals can be recognized at 14.8 +/- 1.6 (mean +/- SD) days of age and die within 35 days after birth. There are no sex differences in phenotype. The breeding data suggest that the abnormal locomotion is caused by an autosomal recessive gene. We have tentatively named the gene creeping (cre). The cerebellum of affected rats is much smaller than that of normal littermates. The cerebellar lobes of the mutant are barely formed. The notable histopathological changes are disarrangement of neuronal cells in the cerebellum and cerebral cortices, although the several cell types that are present in the cortices of normal rats are also found in the cortex of the creeping rats. The same type of change is also present in the hippocampus and fascia dentata.

Animals↗
PubMed1988

Alteration of insulin and glucagon secretion from the perfused BB rat pancreas before and after the onset of diabetes.

Secretion of insulin and glucagon from perfused BB rat pancreas was examined in rats (5 weeks old; n = 6) before and 2 weeks after (13 weeks old; n = 5) the onset of diabetes mellitus. The secretion of insulin and glucagon was modified by increasing concentrations of glucose in the perfusate from 2.8 mM to 16.5 mM. In 5-week-old BB rats, glucagon secretion was higher at the low glucose concentration (2.8 mM) and insulin secretion lower at the high glucose concentration (16.5 mM) than the corresponding values in age-matched control rats. In 13-week-old BB rats, insulin secretion was undetectable irrespective of glucose concentration. Glucagon secretion was only moderately suppressed by the perfusion of high glucose (16.5 mM) and was significantly higher than that of age-matched controls. The reduction in insulin secretion observed in 5-week-old rats without insulitis indicated that pancreatic B cells of BB rats of this age are somehow injured by humoral factors rather than cell infiltration. Cell function was apparently modified indirectly by the destruction of neighboring B cells.

Aging↗
PubMed1988

Effects of cyclosporin A and insulin on peripheral lymphocytes in BB/W rats.

The effects of cyclosporin A (Cs-A) and insulin on peripheral lymphocytes in BB/W rats were studied. The cumulative incidence of overt diabetes in untreated BB/W rats was 72% up to 120 days of observation, whereas the incidence was 13% in Cs-A-treated rats. Lymphocytopenia, consisting of decreased OX19+ (pan T), W3/25+ (helper/inducer T) and OX8+ (cytotoxic/suppressor T) cells, was present in BB/W rats. Cs-A significantly decreased both the percentage and the absolute number of OX8+, OX6+ (Ia-positive) and OX12+ (B) cells, and augmented the ratio of W3/25+ to OX8+ cells in BB/W rats. On the other hand, insulin injection significantly decreased the percentage of OX6+ cells and the ratio of W3/25+ to OX8+ cells in BB/W rats. Thus, rearrangement of the ratio of helper/inducer T to cytotoxic/suppressor T cells and reduction in the number of Ia antigen-bearing cells could be important for the inhibitory effects of diabetes in BB/W rats upon treatment with Cs-A or insulin.

Animals↗
PubMed1986

Spontaneous autoimmune thyroiditis in Bio Breeding/Worcester (BB/W) rat.

We investigated the serial changes in the plasma levels of anti-thyroglobulin antibody (ATA) by solid-phase enzyme immunoassay, thyroid hormones and blood glucose, since spontaneous occurring lymphocytic thyroiditis (LT) has been found in spontaneously diabetic Bio Breeding/Worcester (BB/W) rat. We also observed the correlation between these levels and histological findings in the thyroid gland. The incidence of diabetes was 0% in 5 week old rats (group A), 70% in 11 week old rats (group B), and 86% in 20 week old rats (group C), while LT was observed in 0% in group A, 20% in group B and 48% in group C. Although the incidence of both increased with age, there was no link between LT and diabetes. Plasma ATA levels were 91.4 +/- 28.5 (OD492 X 1,000, mean +/- SEM) in the control (14 week old Wistar Furth) rats. 49.5 +/- 15.4 in group A, 197.8 +/- 41.5 in group B, and 376.7 +/- 48.7 in group C, again showing a clear increase with age. In group C, the plasma levels of ATA in rats with LT were significantly higher than those without LT. In addition, 6 out of 11 rats without LT had abnormaly high ATA levels. In group C, the plasma levels of free 3,5,3'-triiodothyronine (FT3) and total thyroxine (TT4), and also the FT3/TT4 ratio were significantly lower and the plasma levels of blood glucose were higher than in the other groups. There was no difference between the plasma thyroid hormone levels in rats with LT and those without LT. These studies suggest that LT may occur independently of insulitis, namely diabetes, ATA levels and the incidence of LT increase with age, the site of ATA production may not be confined to the thyroid gland, and the derangement of glucose metabolism may be one of the factors in the decrease in plasma thyroid hormone. The BB/W rat is not only a useful animal model to use in exploring the pathogenesis of human insulin-dependent diabetes mellitus, but also spontaneous autoimmune thyroiditis.

Age Factors↗
PubMed1984

Non-obese-diabetic mice: immune mechanisms of pancreatic beta-cell destruction.

The sequence of events shortly before the initiation of diabetes in female non-obese diabetic mice was studied. Immunologically, anti-lymphocyte antibodies appeared most frequently at 3 weeks of age and decreased thereafter. Insulin concentrations dropped after the initiation of mononuclear cell infiltration into the islets. The majority of female mice lost approximately 85% of their insulin at aged 22 weeks. Islet cell surface antibodies appeared most frequently during this period (12-18 weeks). Morphological examination revealed that mononuclear cells start to infiltrate islets at 6 weeks of age and involve major areas of the islets in females aged 22 weeks. Among these mononuclear cells, IgM-positive cells were found to be a major constituent, forming follicular (nodular) cell aggregates. T-helper and/or T-cytotoxic cells (Lyt-1-, and/or Lyt-2-positive cells) were fewer and located mainly around the follicular structures. Asialo GM 1-positive lymphocytes (natural killer cells), though present, were far fewer. The process of destruction of pancreatic islets in non-obese diabetic mice is discussed with emphasis on the characteristic local immune response in the pancreas.

Animals↗