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N Hotta

Publications and source records attributed to N Hotta.

At least 91 records · Page 5Linked to original sources
PubMed1997

Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats: an inhibitory effect of biguanides.

To examine the pathophysiological characteristics of non-insulin-dependent diabetes mellitus, alanine metabolism in isolated hepatocytes of male Wistar-Kyoto (WKY) fatty rats (genetically obese and hyperglycemic) and their lean littermates was investigated. The effects of glucagon and the biguanides, metformin and buformin, on alanine metabolism were also studied by measuring alanine uptake and lipid synthesis from alanine. WKY fatty rats showed higher plasma insulin and lipid concentrations than lean rats at 5 as well as at 12 weeks of age. Alanine uptake into hepatocytes was increased in fatty rats only at 12 weeks of age compared with lean rats. Lipid synthesis from alanine in hepatocytes was increased in fatty rats at 5 and 12 weeks of age compared with lean rats. Glucagon increased alanine uptake into hepatocytes but did not affect lipid synthesis from alanine in both fatty and lean rats. Low concentrations (0.1 mM) of biguanides decreased lipid synthesis from alanine only in fatty rats without inhibiting alanine uptake into hepatocytes. These observations suggest that lipid synthesis from alanine in hepatocytes of WKY fatty rats is accelerated prior to the onset of diabetes mellitus, which might be associated with the development of diabetes, and that an inhibitory effect on increased lipid synthesis is one of the pharmacodynamic actions of biguanides.

Aging↗
PubMed1997

Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis.

The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage.

Animals↗
PubMed1997

[Voglibose].

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Administration, Oral↗
PubMed1997

[Epalrestat].

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Aldehyde Reductase↗
PubMed1997

New concepts and insights on pathogenesis and treatment of diabetic complications: polyol pathway and its inhibition.

The polyol pathway is one of the possible biochemical mechanisms by which hyperglycemia could impair the function and structure of the cells affected by diabetic complications. As possible hypothesis for the pathogenesis of diabetic complications, the polyol osmotic theory, alterations in myo-inositol and sodium metabolism, intermediary metabolites, abnormal changes of the redox state (NADH/NAD+ ratio) and an abnormality of kinase C dependent protein phosphorylation have been proposed. Recently, increasing evidence suggests that glycation and oxidative stress may have a cross-link with polyol pathway, contributing to the development of diabetic complications. If hyperglycemia-induced polyol pathway hyperactivity has an important role in the etiology of late-onset diabetic complications, the inhibition of aldose reductase (AR), a rate-limiting enzyme of the pathway, could become a key element in the prevention and reversal of diabetic complications. Recent evidence from both animal experiments and clinical studies has emerged to support this theory, resulting in the development of drugs available for the clinical treatment of diabetic neuropathy. From the results obtained mainly in animal models of diabetic complications, it is well recognized at present that AR inhibitors have a positive inhibitory effect on neuropathy, retinopathy, nephropathy, keratopathy, cataract-formation, possibly infection and atherosclerosis. It is now clear that AR inhibitors may offer various benefits to patients with diabetic complications. However, more extensive efforts are needed for the evaluation of their effects.

Animals↗
PubMed1996

Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway.

To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.

Animals↗
PubMed1996

Nerve function and blood flow in Otsuka Long-Evans Tokushima Fatty rats with sucrose feeding: effect of an anticoagulant.

To investigate the pathogenesis of diabetic neuropathy in non-insulin-dependent diabetes mellitus, Otsuka Long-Evans Tokushima Fatty rats, an animal model of non-insulin-dependent diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka rats were fed with or without sucrose and/or cilostazol, an anticoagulant, for 8 weeks. Sucrose-fed diabetic rats showed a delayed motor nerve conduction velocity, decreased R-R interval variability of electrocardiogram, reduced sciatic nerve blood flow, increased platelet aggregability and a decreased erythrocyte 2,3-diphosphoglycerate concentration compared with non-sucrose-fed diabetic rats and non-diabetic rats. These abnormalities were significantly prevented by treatment with cilostazol without changes in the nerve tissue levels of polyols. These findings indicate that sucrose-fed Otsuka Long-Evans Tokushima Fatty rats may be a useful animal model of neuropathy in non-insulin-dependent diabetes mellitus, and that cilostazol may prevent the development of diabetic neuropathy by modifying vascular factors.

2,3-Diphosphoglycerate↗
PubMed1996

Effect of propionyl-L-carnitine on oscillatory potentials in electroretinogram in streptozotocin-diabetic rats.

The effect of propionyl-L-carnitine, an analogue of L-carnitine, and insulin on the oscillatory potentials of the electroretinogram was determined in rats with streptozotocin-induced diabetes. Propionyl-L-carnitine was administered at a daily dose of 0.5 g/kg by gavage for 4 weeks, while other rats were treated with subcutaneous injections of insulin (8-10 U/day). Both treatments shortened the peak latencies of the oscillatory potentials in the electroretinogram, which were significantly prolonged in untreated diabetic rats (O1, O2 and O3, and sigma (O1 + O2 + O3)) (P < 0.0001 vs. untreated normal rats). A significant decrease in the erythrocyte free carnitine level in diabetic rats was prevented by both treatments. Insulin produced a significant reduction of retinal glucose, sorbitol and fructose levels in diabetic rats, while propionyl-L-carnitine failed to do so. However, both treatments markedly reduced serum lipids levels in the diabetic rats. These findings provide information on the pathogenesis of diabetic retinopathy as well as suggesting the potential therapeutic value of propionyl-L-carnitine for retinopathy.

Analysis of Variance↗
PubMed1996

Effects of long-term enalapril treatment on persistent microalbuminuria in normotensive type 2 diabetic patients: results of a 4-year, prospective, randomized study.

The beneficial effect of long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor on urinary microalbumin excretion (UAE) and renal function was investigated in a 4 year, randomized prospective study in normotensive patients with non-insulin-dependent (Type 2) diabetes mellitus. Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were randomized to receive either enalapril 5 mg day-1 or no treatment. In the enalapril-treated patients, UAE was reduced from 115.4 +/- 80.1 to 95.6 +/- 61.7 mg 24 h-1 after 12 months (p < 0.05) and to 75.3 +/- 44.8 mg 24 h-1 after 48 months (p < 0.001). In the untreated group, UAE increased slowly from 93.9 +/- 69.9 to 150.0 +/- 144.5 mg 24 h-1 after 48 months. No changes in creatinine clearance, blood pressure or HbA1C were seen in either group during the 4-year period. In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria. This effect is long-lasting and probably independent of the antihypertensive action of the drug.

Aged↗
PubMed1996

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

The effect of an analogue of L-carnitine, propionyl-L-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-L-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8-10 U daily for 4 weeks), propionyl-L-carnitine and combined therapy. Although propionyl-L-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-L-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl-L-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.

Animals↗
PubMed1996

Enhancement and inhibition of mitogenic action of insulin-like growth factor I by high glucose in cultured bovine retinal pericytes.

To explore the possible relationship between insulin-like growth factor I(IGF-I) and diabetic retinopathy, we examined the effects of glucose on IGF-I stimulated thymidine incorporation into DNA and IGF-I binding in cultured bovine retinal pericytes. IGF-I significantly increased thymidine incorporation, and its effect was completely inhibited by IGF-I receptor antibody. The exposure to high glucose for 8 h significantly enhanced the IGF-I induced increase in thymidine incorporation as compared with those to normal glucose and to high osmolarity. In contrast, the incubation with high glucose for 24 h decreased thymidine incorporation in response to IGF-I. Specific binding of IGF-I to pericytes was increased by the incubation with high glucose for both 8 and 24 h. These results suggest that glucose may play an important role in the regulation of mitogenic action of IGF-I in retinal pericytes.

Animals↗
PubMed1996

The reduction and redistribution of plantar pressures using foot orthoses in diabetic patients.

High pressures on the soles of the feet of diabetic patients cause plantar ulcerations, and reduction of this pressure is important in the treatment and prevention of such ulcers. The effects of foot orthoses on the distribution of plantar pressures were investigated using a pressure-sensitive insole containing 960 sensor elements in seven diabetic patients (13 feet) with diabetic ulcers or past histories of diabetic ulcers. Plantar pressures at the foot-insole interface and their distribution were measured in a stable standing position wearing the patients' own shoes, with and without foot orthoses. The preorthotic peak pressure was 130.6 +/- 41.9 kPA (mean +/- S.D.), while the postorthotic peak pressure was reduced to 52.6 +/- 17.9 kPa (P < 0.001 vs. preorthotic). The mean reduction of pressure was 56.3%. The preorthotic contact area was 330.2 +/- 48.4 pressure-sensitive elements and the postorthotic contact area was increased to 517.2 +/- 105.5 elements (P < 0.001), with a mean increase of 62.7%. The marked reduction in plantar pressures at the foot-insole interface by pressure redistribution indicates that this new pressure measurement system is very useful for the design of such orthoses.

Adult↗
PubMed1996

Effect of acarbose on blood glucose profiles and plasma 1,5-anhydro-d-glucitol in type 2 diabetes poorly controlled by sulfonylurea therapy.

Sixteen patients with type 2 diabetes poorly controlled by glibenclamide (7.5-10.0 mg/day) were treated with acarbose (100 mg tds) for one week and the effect on the blood glucose profile, 24-hour urinary glucose excretion, plasma fructosamine, and plasma 1,5-anhydro-D-glucitol (1,5-AG) level was determined. The blood glucose profile was more stable and levels were lower during acarbose administration. In some patients, this improvement was maintained after discontinuing acarbose. The M-value, an indicator of blood glucose fluctuations, decreased significantly from 33.2 +/- 3.0 (mean +/- SEM) in the run-in period to 13.4 +/- 2.4 during acarbose therapy (P < 0.001), and rose again to 26.5 +/- 4.4 (P < 0.001) in the follow-up period. The 24-hour urinary glucose excretion and plasma fructosamine decreased similarly (P < 0.001 and P < 0.01, respectively) during and after acarbose therapy. Plasma 1,5-AG levels did not change significantly during acarbose therapy, but increased markedly afterwards (from 19.3 +/- 3.1 mumol 1(-1) to 25.0) +/- 3.1 mumol l-1, P < 0.001). Plasma 1,5-AG levels were significantly correlated with urinary glucose excretion one week earlier (r = 0.513, P < 0.006). These findings suggest that acarbose may improve glycemic control in type 2 diabetic patients poorly controlled by sulfonylurea therapy and that plasma 1,5-AG might be used as a marker of glycemic control cooperating with other markers such as fructosamine and urinary glucose determination for monitoring the short-term response to antidiabetic therapy.

Acarbose↗