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Biomedical subjects

Y Seino

Publications and source records attributed to Y Seino.

At least 19 recordsLinked to original sources

Factors responsible for glucose intolerance in Japanese subjects with impaired fasting glucose.

Impaired fasting glucose (IFG) represents risk of development of diabetes (DM) and its complications. We investigated insulin secretion and insulin sensitivity in 403 IFG subjects divided into three levels of 2-hour postchallenge glucose (2-h PG) to clarify the factors responsible in the development of glucose intolerance in Japanese IFG. Nearly 60% of the subjects at annual medical check-up with FPG of 6.1-7.0 mmol/l at the first screening were diagnosed by 75 g oral glucose tolerance test (OGTT) to have impaired glucose tolerance (IGT; FPG <7.0 mmol/l and 7.8 mmol/l <2-h PG <11.1 mmol/l) or DM (isolated postchallenge hyperglycemia (IPH); FPG <7.0 mmol/l and 11.1 mmol/l <2-h PG level). The primary factor in the decreased glucose tolerance was a decrease in early-phase insulin, with some contribution of increasing insulin resistance. In addition, IFG/IGT and IFG/IPH subjects showed a compensatory increase in basal insulin secretion sufficient to keep FPG levels within the non-diabetic range. IFG is composed of three different categories in basal, early-phase insulin secretion, and insulin sensitivity.

Asian People↗

Electromyography of the cricoarytenoid unit during supracricoid laryngectomy with a cricohyoidoepiglottopexy procedure.

Two patients who received supracricoid laryngectomy with cricohyoidoepiglottopexy to treat laryngeal cancers, underwent intra-operative electromyography analysis. After the lesion was removed and the electrodes were inserted into the remaining intrinsic laryngeal muscles, the depth of anaesthesia was carefully reduced. Gentle tactile stimulations were applied to the pharynx to trigger the reflex movement of the remaining arytenoids. Recordings were made when reflex movement was achieved. Case one: Electromyography (EMG) of the remaining arytenoid demonstrated clear phase differences indicating reciprocal activities between the adductor group (lateral cricoarytenoid muscle, interarytenoid muscle) and the abductor muscle (posterior cricoarytenoid muscle). Case two: EMG of the remaining arytenoid demonstrated reciprocal activities between the interarytenoid muscle and the posterior cricoarytenoid muscle. Activity of the lateral cricoarytenoid muscle was not evident because the muscle was excised during removal of the paraglottic space. Mobility of the arytenoid was attributed to interaction between the interarytenoid muscle and posterior cricoarytenoid muscle. Reciprocal interaction between the interarytenoid muscle and posterior cricoarytenoid muscle alone is also capable of maintaining post-operative laryngeal functions after supracricoid laryngectomy with cricohyoidoepiglottopexy.

Aged↗

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets.

We have established a new method for allogeneic pancreatic islet (PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1A(l), RT1B(l)), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1A(n), RT1B(n)) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of '9 Gy+IBM'(10/10 accepted), '9 Gy+PV'(7/10 accepted), '9 Gy+IV'(0/7 accepted), '9 Gy+PV+IBM'(8/8 accepted), '8.5 Gy+IBM'(4/9 accepted), '8.5 Gy+PV'(0/7 accepted), '8.5 Gy+IV'(0/7 accepted), '8.5 Gy+PV+IBM'(9/12 accepted), '8 Gy+IBM'(2/10 accepted) and '8 Gy+PV+IBM'(2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable strategy.

Animals↗

Effect of corosolic acid on postchallenge plasma glucose levels.

Corosolic acid (CRA) is a substance extracted from Lagerstroemia speciosa L. and has been reported to have biological activities in in vitro and experimental animal studies. In this study, 31 subjects were orally administered 10mg CRA or a placebo, on different occasions, in a capsule 5min before the 75-g oral glucose tolerance test (OGTT) in a double-blind and cross-over design. Nineteen subjects had diabetes, seven had impaired glucose tolerance, one had impaired fasting glucose, and four had normal glucose tolerance according to the 1998 WHO criteria. There were no significant differences in plasma glucose levels before and 30min after the administration. CRA treatment subjects showed lower glucose levels from 60min until 120min and reached statistical significance at 90min. In this study, we have shown for the first time that CRA has a lowering effect on postchallenge plasma glucose levels in vivo in humans.

Blood Glucose↗

Periodontal infection and dyslipidemia in type 2 diabetics: association with increased HMG-CoA reductase expression.

Recent studies have suggested that the periodontal disease, chronic sub-clinical inflammation, is associated with atherosclerosis, although "cause or effect" relationship is still unclear. The aim of this study was to assess the association between the degree of periodontal infection and lipid profiles in diabetic subjects. Additionally, the association of such sub-clinical inflammation with HMG-CoA reductase gene expression was evaluated. One hundred and thirty-one non-obese relatively well-controlled Japanese type 2 diabetic patients were enrolled for the study. Although no significant association was observed between serum triglycerides, HLD-cholesterol and antibody titer to Porphyromonas gingivalis (Pg), the most predominant periodontal pathogen in adults, LDL-cholesterol was significantly associated with antibody titer to Pg. Concomitantly, the same works out to be true for total cholesterol. To understand the possible mechanisms underlying this association, we evaluated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase gene expression in cultured HepG2 cells stimulated by either bacterial lipopolysaccharide (LPS) or inflammatory cytokines. Although Pg and E. coli LPS had no effect on HMG-CoA reductase gene expression, both tumor necrosis factor-alpha and interleukin-6 (IL-6), especially IL-6 at low concentration, markedly up-regulated HMG-CoA reductase gene expression. It can be concluded that Pg infection is associated with increased LDL-cholesterol in diabetic subjects, which may be accompanied by increased cholesterol synthesis by inflammatory cytokines.

Adult↗

Soluble TNF receptors and albuminuria in non-obese Japanese type 2 diabetic patients.

The aim of this study was to investigate the relationships between albuminuria and tumor necrosis factor (TNF)-alpha or soluble TNF receptors (sTNF-R1, sTNF-R2) in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two groups according to albuminuria status-microalbuminuria or normoalbuminuria. Patients with microalbuminuria were older and had significantly higher concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There was, however, no significant difference in sex, diabetes duration, smoking, BMI, systolic and diastolic blood pressure, HbA (1c), serum creatinine, and lipid profile between the two groups. Although serum TNF-alpha was positively correlated to serum sTNF-R1 and sTNF-R2, serum TNF-alpha level did not differ with respect to albuminuria. Univariate regression analysis showed that urinary albumin concentration was positively correlated to age (r=0.380, p<0.001), serum creatinine (r=0.214, p<0.05) and concentrations of sTNF-R1 (r=0.364, p<0.001) and sTNF-R2 (r=0.342, p<0.005). Other variables, including TNF-alpha, were not associated with albuminuria. Multiple regression analyses showed that urinary albumin concentration was independently predicted by the level of sTNF-R1 (F=32.1), which explained 26.3% of the variability of urinary albumin concentration. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with albuminuria in non-obese Japanese type 2 diabetic patients.

Aged↗

Osteoclastogenesis inhibitory factor/osteoprotegerin reduced bone loss induced by mechanical unloading.

Skeletal unloading resulting from space flight and prolonged immobilization causes bone loss. Such bone loss ostensibly results from a rapid increase in bone resorption and subsequent sustained reduction in bone formation, but this mechanism remains unclear. Osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) is a recently identified potent inhibitor of osteoclast formation. We studied effects of OPG administration on tail-suspended growing rats to explore the therapeutic potential of OPG in the treatment and prevention of bone loss during mechanical unloading, such as that which occurs during space flight. Treatment with OPG in tail suspension increased the total bone mineral content (BMC g) of the tibia and femur and the total bone mineral density (BMD g/cm2) of the tibia. Moreover, treatment with OPG prevented reduction not only of BMC and BMD, but also of bone strength occurring through femoral diaphysis. Treatment with OPG in tail-suspended rats improved BMC, BMD and bone strength to levels of normally loaded rats treated with vehicle. Treatment with OPG in normally loaded rats significantly decreased urinary excretion of deoxypyridinoline, but the effect of OPG in tail suspension was unclear. These results indicate that OPG may be useful in inhibiting bone loss-engendered mechanical unloading.

Amino Acids↗

Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes.

To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan, insulin secretion and insulin sensitivity were compared across the range of glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to the criteria of the World Health Organization (WHO). We examined insulin secretion and insulin sensitivity using fasting blood glucose and insulin levels and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI) composite for insulin sensitivity. Although insulin resistance plays an important role in the development of diabetes in many ethnic populations, the differences in insulin sensitivity between NGT and IGT and between IGT and DM are small in Japanese patients. On the other hand, as glucose intolerance increases, insulin secretion decreases most remarkably both between NGT and IGT and between IGT and DM in Japanese patients. Decreasing insulin secretion and decreasing insulin sensitivity both occur in developing type 2 diabetes in Japanese patients, but decreased basal and early-phase insulin secretion had more pronounced contribution to glucose tolerance than the indices of insulin sensitivity. Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance.

Aging↗

Prevalence of periodontal bacterial infection in non-obese Japanese type 2 diabetic patients: relationship with C-reactive protein and albuminuria.

The aim of the present study was to investigate the relationship between periodontal bacteria infection ( Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedius) and C-reactive protein (CRP) and albuminuria in non-obese Japanese type 2 diabetic patients. One hundred and thirty-four non-obese Japanese type 2 diabetic patients without evidence of current acute illness including clinically significant acute infectious disease were enrolled into the study. The degree of periodontal bacterial infection was evaluated using IgG titer against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, or Prevotella intermedius. The bacterial sonic extracts were used as antigens. High-sensitivity CRP (hCRP), glucose, glycosylated hemoglobin (HbA (1c)), and lipids were also measured after an overnight fast. Urinary albumin excretion rate as a ratio of urinary albumin and urinary creatinine was assessed in a morning spot urine sample using a commercial enzymatic immunoassay. The prevalence of Porphyromonas gingivalis infection was 52.2 % and that of Actinobacillus actinomycetemcomitans and Prevotella intermedius was 7.5 and 14.2 %, respectively. IgG titer against Porphyromonas gingivalis significantly correlated with CRP (r = 0.225, p < 0.001) and albuminuria (r = 0.185, p < 0.05), while IgG titer against Actinobacillus actinomycetemcomitans or Prevotella intermedius was not associated with either parameter. These results suggest that among periodontal bacteria, Porphyromonas gingivalis infection is associated with atherosclerosis in non-obese Japanese type 2 diabetic patients.

Actinobacillus Infections↗

Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats.

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.

Alkaline Phosphatase↗

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗

Beneficial effect of pretreatment of islets with fibronectin on glucose tolerance after islet transplantation.

The scarcity of available islets is an obstacle for clinically successful islet transplantation. One solution might be to increase the efficacy of the limited islets. Isolated islets are exposed to a variety of cellular stressors, and disruption of the cell-matrix connections damages islets. We examined the effect of fibronectin, a major component of the extracellular matrix, on islet viability, mass and function, and also examined whether fibronectin-treated islets improved the results of islet transplantation. Islets cultured with fibronectin for 48 hours maintained higher cell viability (0.146 +/- 0.010 vs. 0.173 +/- 0.007 by MTT assay), and also had a greater insulin and DNA content (86.8 +/- 3.6 vs. 72.8 +/- 3.2 ng/islet and 35.2 +/- 1.4 vs. 30.0 +/- 1.5 ng/islet, respectively) than islets cultured without fibronectin (control). Absolute values of insulin secretion were higher in fibronectin-treated islets than in controls; however, the ratio of stimulated insulin secretion to basal secretion was not significantly different (206.9 +/- 23.3 vs. 191.7 +/- 20.2% when the insulin response to 16.7 mmol/l glucose was compared to that of 3.3 mmol/l glucose); the higher insulin secretion was thus mainly due to larger islet cell mass. The rats transplanted with fibronectin-treated islets had lower plasma glucose and higher plasma insulin levels within 2 weeks after transplantation, and had more favorable glucose tolerance 9 weeks after transplantation. These results indicate that cultivation with fibronectin might preserve islet cell viability, mass and insulin secretory function, which could improve glucose tolerance following islet transplantation.

Animals↗

Normalization of cytoplasmic calcium response in pancreatic beta-cells of spontaneously diabetic GK rat by the treatment with T-1095, a specific inhibitor of renal Na+-glucose co-transporters.

Chronic hyperglycemia is known to lead to a progressively further impaired insulin response and to hasten the development of complications in patients with type 2 diabetes, a notion referred as glucose toxicity. T-1095, a derivative of phlorizin, is a newly developed oral hypoglycemic agent that acts as a specific inhibitor of renal Na(+)-glucose co-transporters, reducing circulating blood glucose levels by promoting glucose excretion into urine. The effects of glycemic improvement by T-1095 on secretory function and cytoplasmic calcium response in pancreatic beta-cells were investigated using spontaneously diabetic GK rats. After four weeks of treatment with T-1095 (age 4 to 8 week rats), serum glucose and HbA1c levels were significantly improved (serum glucose level, GK vs. GK T-1095, 277.3 +/- 11.8 vs. 204.7 +/- 6.4 mg/dl; HbA1c level, GK vs. GK T-1095, 6.2 +/- 0.2 vs. 4.8 +/- 0.1 %). Insulin secretion induced by 16.7 mM glucose was also significantly increased in the T-1095-treated group compared to the untreated group. The [Ca(2+)]i response induced by 16.7 mM glucose in GK beta-cells was characterized by the loss of the steep first peak of [Ca(2+)]i elevation, and the lost first peak of [Ca(2+)]i reappeared in T-1095-treated beta-cells in 32 of 34 observations. In T-1095-treated beta-cells, the time lag to peak [Ca(2+)]i levels in the 16.7 mM glucose stimulation was significantly reduced (259.1 +/- 15.3 sec, p < 0.01) compared to untreated GK rats (524.7 +/- 52.9 sec). Thus, improvement of hyperglycemia by T-1095 ameliorates beta-cell function by relieving [Ca(2+)]i response.

Animals↗

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.

BACKGROUND/AIMS: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted. METHOD: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions. RESULTS: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups. CONCLUSION: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.

Adult↗