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Biomedical subjects

F Sakakibara

Publications and source records attributed to F Sakakibara.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

An importance of carbohydrate ingestion for the expression of the effect of alpha-glucosidase inhibitor in NIDDM.

OBJECTIVE: To examine the usefulness of alpha-glucosidase inhibitors in glycemic control of patients with NIDDM. The involvement of carbohydrate ingestion in manifestation of the effects of alpha-glucosidase inhibitors was also investigated. RESEARCH DESIGN AND METHODS: A total of 41 patients hospitalized with NIDDM (22 patients receiving sulfonylurea and 19 receiving insulin therapy) were given alpha-glucosidase inhibitors during the period when their blood glucose levels were well controlled. They were followed for 3 weeks as inpatients and for an additional 6 months as outpatients. They were retrospectively divided into two groups according to the percentage of carbohydrates in all sources of calories during outpatient management: the < 50% group and the > 50% group. Between these two groups, we compared circadian variation in blood glucose levels, HbA1c, and urine C-peptide. RESULTS: Treatment with alpha-glucosidase inhibitors during the hospital stay markedly improved circadian variation in blood glucose levels and HbA1c and decreased urine C-peptide in both groups. While HbA1c returned to its pretreatment level at 6 months after the treatment in the < 50% group, HbA1c had further improved in the > 50% group at 6 months. CONCLUSIONS: alpha-Glucosidase inhibitors are useful for glycemic control in patients with NIDDM and the percentage of carbohydrate in all calorie sources is an important factor for the expression of their effects.

Biomarkers↗
PubMed1996

Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor.

The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.

Aldehyde Reductase↗
PubMed1995

Polyol pathway, 2,3-diphosphoglycerate in erythrocytes and diabetic neuropathy in rats.

The relationship between the 2,3-diphosphoglycerate concentration in red blood cells as a biological indicator of tissue hypoxia and diabetic neuropathy, and the effect of a potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2'5'-dioxospiro [chroman-4,4'-imidazolidine]-2-carboxamide (SNK-860), on both were investigated in streptozotocin-induced diabetic rats. Diabetic rats demonstrated significantly delayed motor nerve conduction velocity and reduced sciatic nerve blood flow. Altered biochemical features in the sciatic nerves, including a marked accumulation of sorbitol and fructose, myo-inositol depletion and decreased Na+/K(+)-ATPase activity were also detected in diabetic rats. These defects were accompanied by a decrease in the red blood cell 2,3-diphosphoglycerate concentration. Treatment with SNK-860 partially or completely ameliorated these abnormalities. These observations suggest that a decrease in the red blood cell 2,3-diphosphoglycerate concentration is one of the factors contributing to tissue hypoxia, which results in diabetic neuropathy, and that this decrease is mediated through an aldose reductase inhibitor-sensitive pathway.

2,3-Diphosphoglycerate↗
PubMed1995

Effects of an aldose reductase inhibitor on erythrocyte fructose 3-phosphate and sorbitol 3-phosphate levels in diabetic patients.

Fructose 3-phosphate and sorbitol 3-phosphate are novel metabolites that have been shown to associate with the polyol pathway in animal experiments. Fructose 3-phosphate is of particular interest because of its potent glycation capability as compared with other glycolytic intermediates, e.g., fructose. We observed the effects of treatment with epalrestat, an aldose reductase inhibitor, on their concentrations in erythrocytes from diabetic patients. The levels of both metabolites were significantly higher in diabetic patients than in non-diabetic subjects. A group of patients who had been treated with epalrestat showed significantly lower levels of both metabolites as compared with those untreated. A treatment of three patients with epalrestat for one month resulted in obvious decreases in their concentrations. The results suggest a possible explanation for the preventive effect of an aldose reductase inhibitor on nonenzymatic glycation.

Adult↗
PubMed1995

Neurotropin prevents neurophysiological abnormalities and ADP-induced hyperaggregability in rats with streptozotocin-induced diabetes.

Neurotropin, a non-proteinaceous extract from the inflamed dermis of rabbits inoculated with vaccinia virus, was administered for 8 weeks to rats with streptozotocin-induced diabetes. The physiological and biochemical changes of the nerves were studied as well as ADP-induced platelet aggregation. Neurotropin improved the caudal motor nerve conduction velocity, R-R variability, sciatic nerve blood flow, and platelet hyperaggregability in diabetic rats, despite having no effect on sorbitol and fructose accumulation or myoinositol depletion in the sciatic nerve. The correlation between nerve conduction velocity, R-R variability, nerve blood flow, and platelet aggregation were significant between each two parameters (p < 0.0001). Thus, the mechanism of action of neurotropin differed from that of aldose reductase inhibitors. These findings suggest that vascular factors may play an important role in the development of diabetic neuropathy, and that neurotropin may be useful for the treatment of this condition.

Adenosine Diphosphate↗
PubMed1995

Prevention of abnormalities in motor nerve conduction and nerve blood-flow by a prostacyclin analog, beraprost sodium, in streptozotocin-induced diabetic rats.

The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly (P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium (P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.

Animals↗
PubMed1995

Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats.

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.

Aldehyde Reductase↗
PubMed1995

Interference by gliclazide in the glucose oxidase/peroxidase method for glucose assay.

Gliclazide interferes with the glucose determination using the glucose oxidase/peroxidase (EC 1.1.3.4/1.11.1.7) (GOD-PERID) method utilizing 2,2-azino-di-(3-ethyl-benzothiazoline-6-sulphonic acid) (ABTS) as the oxygen acceptor chromogen. There was an essentially linear relationship between the concentrations of gliclazide and decreasing glucose readings. One mu mol/1 of gliclazide in samples leads to an apparent loss of about 2.5 mu mol/l of glucose. However, gliclazide did not interfere with the glucose determination using the hexokinase/glucose-6-phosphate dehydrogenase method. This interference in the GOD-PERID method for glucose assay can occur in the in vitro experimental samples and cause underestimation of the glucose values. It is suggested that careful attention should be paid to the limited applicability of the GOD-PERID method for glucose assay.

Animals↗
PubMed1995

An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP-induced hyperaggregability in streptozotocin-induced diabetic rats.

Rats with streptozotocin-induced diabetes were oral given TAT, a potent aldose reductase inhibitor, at a dose of 10 mg kg-1 day-1 or 40 mg kg-1 day-1 for 30 days. Prolongation of the peak latency of oscillatory potentials in the b-wave of the electroretinogram (ERG), which is associated with retinal Müller cell dysfunction, was significantly improved by treatment with TAT as compared with untreated diabetic rats [sigma(O1 + O2 + O3) was 106.8 +/- 1.8 ms in normal controls (NC), 118.2 +/- 1.1 ms in diabetic controls (DC) (P < 0.001 vs. NC), 110.8 +/- 1.5 ms with 10 mg kg-1 TAT (P < 0.001 vs. DC) and 111.4 +/- 1.6 ms with 40 mg kg-1 TAT (P < 0.01 vs. DC)]. The improvement in ERG abnormalities in diabetic rats was accompanied by partial reduction of elevated sorbitol levels in the retina and erythrocytes, and by correction of platelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insights into the pathogenesis of hyperglycaemic retinal dysfunction and contribute to establishing effective therapy for diabetic retinopathy.

Adenosine Diphosphate↗
PubMed1995

Effect of an aldose reductase inhibitor, SNK-860, on deficits in the electroretinogram of diabetic rats.

To determine the effect of an aldose reductase inhibitor, SNK-860, on the worsening of the electroretinogram (ERG) during a diabetic state, rats with streptozotocin-induced diabetes were administered SNK-860 (1 or 4 mg kg-1 orally) daily for 4 weeks. The effectiveness of SNK-860 in prolonging the peak latencies of oscillatory potentials in the b-wave of the electroretinogram of diabetic rats varied between these different waveform components (designated O1, O2 and O3). SNK-860 (4 mg kg-1 day-1) either completely or partially prevented the prolonged peak latencies at O1 and sigma(O1 + O2 + O3). The drug failed to shorten the latency of the O2 and O3 components, and produced only a modest reduction in retinal levels of sorbitol and fructose, with no increase in myo-inositol. There was a significant correlation between the state of the ERG (components O1 and sigma(O1 + O2 + O3)) and the retinal levels of sorbitol and fructose (P < 0.01), but not of myo-inositol. It is concluded that a better understanding of the mechanism by which SNK-860 acts may provide new insight into the pathogenesis of hyperglycaemic retinal dysfunction and help to establish effective therapy for diabetic retinopathy.

Aldehyde Reductase↗
PubMed1995

An aldose reductase inhibitor, TAT, reduces ADP-induced platelet hyperaggregation in streptozotocin-induced diabetic rats with neuropathy.

To investigate the relationship between metabolic and vascular factors, especially polyol pathway and platelet aggregation, in the pathogenesis of diabetic neuropathy, the effects of a novel potent aldose reductase inhibitor, TAT ((5-(3-thienyl) tetrazol-1-yl) acetic acid monohydrate) on adenosine diphosphate-induced platelet aggregation, polyol contents in platelets, motor nerve conduction velocity (MNCV), and sciatic nerve blood flow (SNBF) were examined in streptozotocin-induced diabetic rats. Diabetic rats demonstrated hyperaggregation in response to adenosine diphosphate, accompanied by sorbitol and fructose accumulation and myoinositol depletion in platelets. Treatment with TAT improved these abnormalities in diabetic rats. A delayed MNCV and a reduced SNBF in diabetic rats were normalized by the administration of TAT. These observations suggest that increased polyol pathway activity plays an important role in platelet aggregation in the development of diabetic neuropathy and that aldose reductase inhibitor is useful for the treatment of diabetic neuropathy from the viewpoint not only of metabolic factors but also of vascular factors.

Adenosine Diphosphate↗
PubMed1993

The inhibitory action of buformin, a biguanide on gluconeogenesis from alanine and its transport system in rat livers.

The effect of buformin, a biguanide, on gluconeogenesis from 10 mM alanine in the presence of 143 nM glucagon were studied using isolated rat liver perfusions. In addition, to investigate possible mechanisms of biguanide action, alanine utilization in isolated rat liver perfusion and [3H]alanine uptake in isolated hepatocytes were observed. Buformin (1.85 mM) strongly inhibited gluconeogenesis from alanine in the presence of glucagon in both normal and streptozocin-induced diabetic rat livers. This inhibition was followed by a decrease in alanine utilization. Both of these inhibitory effects of buformin were dose-dependent. [3H]Alanine uptake was significantly inhibited by buformin. The effect of this agent was similar to but weaker than that of ouabain. However, tolbutamide failed to reduce either alanine utilization or [3H]alanine uptake, although this drug significantly inhibited gluconeogenesis from alanine. These data suggest that biguanides may reduce hepatic alanine utilization via the inhibition of Na+/L-alanine transport activity as one possible mechanism, resulting the inhibition of gluconeogenesis from alanine in the presence of glucagon.

3-Hydroxybutyric Acid↗
PubMed1993

The effect of acarbose on blood glucose profiles of type 2 diabetic patients receiving insulin therapy.

Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 +/- 8.7 (SEM) to 16.7 +/- 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 +/- 6.7 (p > or = 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA1C was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met.

Acarbose↗
PubMed1993

Effects of high glucose concentrations and epalrestat on sorbitol and myo-inositol metabolism in cultured rabbit aortic smooth muscle cells.

To clarify the relationship between abnormality of sorbitol and/or myo-inositol metabolism caused by hyperglycemia and diabetic macroangiopathy, we investigated the effects of high glucose concentrations and epalrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit aortic smooth muscle cells. In cells incubated in the presence of 30 mM glucose for 72 h, the sorbitol content increased approximately 4.5-fold, and the myo-inositol level decreased by 55% compared with control values. Kinetic analysis of high-affinity myo-inositol uptake suggested that smooth muscle cells exposed to high glucose concentrations exhibited a noncompetitive type of inhibition characterized by ouabain-sensitive, energy-dependent active transport. Epalrestat blocked glucose-induced changes in sorbitol and myo-inositol metabolism, suggesting that these changes were caused by the accumulation of sorbitol in the cells. These metabolic changes may impair function of smooth muscle cells, contributing to the pathology of diabetic atherosclerosis, especially Mönckeberg's calcific medial sclerosis. The use of an aldose reductase inhibitor may prevent these glucose-induced changes.

Aldehyde Reductase↗
PubMed1992

Effect of niceritrol on streptozocin-induced diabetic neuropathy in rats.

Niceritrol, a drug with peripheral tissue vasodilatory and serum lipid-lowering activity, was administered for 2 mo to rats with streptozocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue. A markedly lower value of approximately 47% in sciatic nerve blood flow (SNBF) was detected in an untreated diabetic (DC) group than in a nondiabetic control group (CC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol, and fructose values were observed in the sciatic nerve and serum lipids. In contrast, a niceritrol-treated diabetic (DN) group had significantly higher SNBF, MNCV, and sciatic nerve myo-inositol values and lower serum triglyceride levels than group DC. No differences between these two groups were noted in glucose, sorbitol, and fructose levels in the sciatic nerve, or in cholesterol and glucose in serum. These findings suggest that niceritrol has a clear inhibitory effect on the development of delayed MNCV in the diabetic rat, which may be due to reduced nerve blood flow and/or decreased nerve myo-inositol levels.

Animals↗
PubMed1990

Amino acid sequence of a lectin from Japanese frog (Rana japonica) eggs.

The complete amino acid sequence and the location of disulfide bonds of a lectin from Japanese frog (Rana japonica) eggs, which specifically agglutinates transformed cells, are presented. The sequence was determined by analysis of peptides generated by digestion of the S-carboxyamidomethylated protein with Achromobacter protease I, or chymotrypsin, and by chemical cleavage with BNPS-skatole or cyanogen bromide. The lectin is a single-chain protein consisting of 111 residues, with a pyroglutamyl residue at the amino terminus. Four disulfide bonds link half-cystinyl residue 19 to 72, 34 to 82, 52 to 97, and 94 to 111. The sequence and the location of the disulfide bonds are highly homologous to those of bull frog (Rana catesbeiana) egg S-lectin. They are also homologous to human angiogenin, a tumor angiogenesis factor, and a family of pancreatic ribonucleases.

Amino Acid Sequence↗