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N Hotta

Publications and source records attributed to N Hotta.

At least 163 records · Page 9Linked to original sources
PubMed1985

Effects of a fructose-rich diet and the aldose reductase inhibitor, ONO-2235, on the development of diabetic neuropathy in streptozotocin-treated rats.

Streptozotocin-diabetic rats were maintained on a 72% fructose diet for 4 weeks and some were treated with an aldose reductase inhibitor (either alrestatin: 0.9 g . kg-1 . day-1 or ONO-2235: 50 mg . kg-1 . day-1). Fructose feeding significantly influenced the development of impaired motor nerve conduction velocity in the diabetic rats and this effect was positively correlated with sorbitol accumulation in the sciatic nerve of diabetic rats maintained on a fructose-rich diet. Treatment with ONO-2235, a new aldose reductase inhibitor, prevented both slowing of motor nerve conduction velocity and elevation of nerve sorbitol concentration. On the other hand, erythrocyte sorbitol levels were significantly correlated to those of the sciatic nerve (r = 0.86, p less than 0.001) and the retina (r = 0.91, p less than 0.001) in these animals. Thus, our findings suggest that increased polyol pathway activity may be related to the pathogenesis of diabetic neuropathy and erythrocyte sorbitol concentrations may prove a useful indicator for the presence of diabetic complications.

Aldehyde Reductase↗
PubMed1985

Effects of aldose reductase inhibitor on retinal microangiopathy in streptozotocin-diabetic rats.

Wistar strain rats were made diabetic by injection of streptozotocin and divided into three groups fed on different diets: conventional solid foods, a fructose-rich diet and a fructose-rich diet mixed with ONO 2235, an aldose reductase inhibitor. The retinas of these rats were examined in flat mount preparations after trypsinization. Microvascular changes such as capillary tortuosity, microaneurysms, pericyte loss, that are typical of diabetic retinal microangiopathy, were seen most frequently in the rats fed on the fructose-rich diet. The rats fed on the fructose-rich diet with ONO 2235 showed much less vascular change than the diabetic rats fed on the conventional food. Electron microscopy of the retina revealed localized thickening of the basement membrane of the retinal capillaries, and this was most frequent in the fructose-fed rats. However, in rats fed on fructose with ONO 2235 the changes of the basement membrane were slight. It was concluded that the aldose reductase inhibitor, ONO 2235, prevented development of diabetic microangiopathy, probably by suppressing the enzymatic activation of aldose reductase in the retina.

Aldehyde Reductase↗
PubMed1983

The features of causes of death in Japanese diabetics during the period 1971-1980.

The principal causes of death among 9,737 diabetics who died in 280 hospitals all over Japan during the period 1971-1980 have been analyzed retrospectively in this study. The main cause of death in Japanese diabetics was vascular complications. The mortality from vascular complications was 41.5%, 37.9% for males and 46.8% for females, increasing with the duration of diabetes and with age. The most interesting findings were of cardiovascular disease which was the cause of death in 12.3% of the subjects in our study as compared to 54.6% of the Joslin Clinic patients (1971). However, our incidence rate was almost twice that reported in Japan in 1967 by Goto (Japan). In contrast, cerebrovascular disease and nephropathy are much more common in Japanese than in American diabetics. Recently cancer has become more common in Japanese diabetics and 25.3% of the deaths have been assigned to it. In contrast, diabetic coma due to hyperglycemia accounted for only 4.1% of deaths. The average life span of Japanese diabetics is still over 10 years shorter than that of non-diabetics.

Adult↗
PubMed1976

Lipolysis as a function of cell numbers and fat content: comparison between isolated rat and dog adipocytes.

The lipolytic responses to dihydroergotamine (5 mug/mi) of isolated rat adipocytes andto epinephrine (50 ng/m1 and 1 mug/m1) of both rat and dog adipocytes were measured over a period of two hours. Glycerol release was calculated as a function of either glycerol ester content or of cell number per incubation vial. The conventional calculation based on glyceride content gave the following results: a) epididymal fat cells from rats weighing less than 160 gm were more sensitive to dihydroergotamine and epinephrine than were fat cells from heavier animals weighing close to 200 gm; b) dog adipocytes from abdominal subcutaneous tissue were less sensitive to eipnephrine than were rat adipocytes. No such differences were noted when the same data were calculated on the basis of cell numbers per incubation vial: the lipolytic response was uniform with rat adipocytes obtained either from the lighter or the heavier weight groups, and so was the response of dog and rat cells. These results indicate that in the type of studies where receptor-dependent hormone and drug effects are measured, the number of cells per incubation vial is an important parameter to be considered in evaluating a lipolytic response.

Abdominal Muscles↗
PubMedDate not supplied

Biguanides may produce hypoglycemic action in isolated rat hepatocytes through their effects on L-alanine transport.

We investigated the mechanisms of the effects of the biguanides metformin and buformin on hepatic gluconeogenesis in hepatocytes isolated from normal rats. Both 10 nM glucagon and 50 microM dibutyryl cAMP increased [3H]alanine uptake in isolated hepatocytes of normal rats by about 150% and 55%, respectively, compared with the effect of 5 mM alanine alone. Metformin (3 mM) reduced glucagon-stimulated [3H]alanine uptake to the level seen with alanine alone; buformin (3 mM) inhibited glucagon-stimulated [3H]alanine uptake by about 69%. The effects of biguanides on dibutyryl cAMP-stimulated [3H]alanine uptake were similar, but of smaller magnitude compared with those observed in the presence of glucagon. Ouabain (3 mM) had a stronger inhibitory effect on [3H]alanine uptake than the biguanides. However, 3 mM tolbutamide failed to suppress [3H]alanine uptake in the presence or absence of glucagon or dibutyryl cAMP. Our results suggest that the inhibition of alanine uptake, related to a reduction in the Na+/L-alanine transport system, is a possible mechanism of biguanide-related inhibition of hepatic gluconeogenesis.

Alanine↗
PubMedDate not supplied

Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats.

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.

2,3-Diphosphoglycerate↗
PubMedDate not supplied

Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan.

A number of diabetic patients with diabetic neuropathy were treated with epalrestat, an aldose reductase inhibitor, since this drug was launched into the market in Japan. More than 5000 patients with diabetic neuropathy who were treated with epalrestat for 3-12 months were treated to analyze the efficacy and the adverse reactions of the drug in this study. The improvement rates of subjective symptoms (i.e., spontaneous pain, numbness, coldness, and hypoesthesia) was 75% (slightly improved or better) and those of nerve function tests (i.e., motor nerve conduction velocity, sensory nerve-conduction velocity, and vibration threshold) 36%. Adverse drug reactions were encountered in 129 cases (2.5%) out of 5249 patients, none of which were severe ones. Although data are limited, they strongly suggest that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.

Adult↗