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Biomedical subjects

R Kikkawa

Publications and source records attributed to R Kikkawa.

At least 181 records · Page 10Linked to original sources
PubMed1986

Impaired contractile responsiveness of diabetic glomeruli to angiotensin II: a possible indication of mesangial dysfunction in diabetes mellitus.

The contractile function of renal glomerulus was studied in vitro using isolated glomeruli from streptozotocin-diabetic rats. Glomerular contraction was assessed by the reduction of extracellular [3H]inulin space of glomerulus, mostly composing of intracapillary space, produced by angiotensin II. The inulin space was dose-dependently reduced after angiotensin II addition in both diabetic and control rats but the degree of reduction significantly smaller in the former. The radioreceptor assay revealed rather increased angiotensin II receptors in diabetic glomeruli. Since the contractile response of glomerulus to angiotensin II is mediated via mesangial cell contraction, these results suggest the presence of mesangial cell dysfunction in diabetes.

Angiotensin II↗
PubMed1986

Effect of angiotensin II infusion on glomerular angiotensin II receptor in rats.

Previous studies by other investigators have shown that sodium depletion causes down-regulation of angiotensin II receptors in renal glomeruli, which is ascribed to elevation of circulating angiotensin II levels. The present study was designed to determine whether elevation of circulating angiotensin II levels alone can down-regulate its own receptors without changes in the sodium balance. Rats were infused with angiotensin II at 50 ng/min intraperitoneally for 24 h or 7 d, then glomeruli were isolated by a mechanical sieving technique and used in a radioreceptor assay for angiotensin II. Angiotensin II infusion for 24 h and for 7 d both significantly suppressed plasma renin activity, and elevated plasma angiotensin II level (3-fold) but did not affect the plasma sodium and potassium or differences between dietary intake and urinary excretion of these electrolytes. By Scatchard analyses significant down-regulation of angiotensin II receptor number was demonstrated in renal glomeruli derived from rats infused with angiotensin II for either 24 h (32% decrease from the control value) or 7 d (37% decrease). No significant changes in receptor affinity were observed after 24 h of angiotensin II infusion, although the infusion for 7 d slightly but significantly decreased Kd (to 2.57 +/- 0.08 nM from 3.17 +/- 0.19, P less than 0.01). From these results, we conclude that circulating angiotensin II level itself can regulate the number of its own receptors in renal glomeruli even in the absence of changes in the sodium balance.

Angiotensin II↗
PubMed1986

Biphasic alteration of renin-angiotensin-aldosterone system in streptozotocin-diabetic rats.

The alteration of renin-angiotensin-aldosterone system caused by diabetes mellitus was studied in streptozotocin-diabetic rats. The plasma renin activity (PRA), and plasma levels of angiotensin II (A II) and aldosterone (PAC) were measured in diabetic and age-matched control rats in 1, 2, 4 and 8 weeks after the intravenous injection of streptozotocin (50 mg/kg body weight). Diabetic rats showed the marked hyperglycemia persistently throughout the experimental period. On 1st week PRA, A II and PAC were significantly increased, and A II and PAC were also significantly elevated on 2nd week in diabetic rats compared with control rats. However, on 4th and 8th weeks PRA, A II and PAC in diabetic rats were significantly lower than those of control rats. Hematocrit values in diabetic rats were elevated on 1st week, normalized on 2nd and 4th weeks and then decreased on 8th week. These results may suggest that the hyperglycemia causes a biphasic alteration of renin-angiotensin-aldosterone system, i.e., early stimulated state due to volume depletion and later suppressed state due to volume expansion.

Aldosterone↗
PubMed1985

The effect of cyproheptadine on insulin biosynthesis.

The effect of a potent antiserotonin-antihistaminic compound, cyproheptadine (CPH) on insulin biosynthesis was studied in pancreatic islets isolated from CPH-treated rats. Though insulin content of islets was markedly reduced in CPH-treated rats, the incorporation of radiolabeled leucine into proinsulin and insulin fractions was not affected with respect to the rate and amount. It is concluded that CPH may deplete insulin content of the islets through causing the leakage of insulin.

Animals↗
PubMed1985

Skin biopsy as a beneficial procedure for morphological evaluation of diabetic neuropathy.

In an attempt to evaluate the morphological abnormalities of dermal non-myelinated nerve fibers of diabetics and elucidate the pathogenesis of diabetic peripheral neuropathy, the terminal part of peripheral nerve in the upper dermis was observed on electron microscopy using skin samples biopsied in 10 diabetics with symptomatic neuropathy and 6 age-matched controls. In diabetics, the density of nerve fibers was significantly lower than in controls. In addition, swelling, lytic change and vacuolation in the axon, multiplication of basement membrane of the Schwann cell and Schwann cell cluster devoid of axon were more frequently observed in diabetics. The Schwann cell did not show significant structural alterations. These findings suggest that the axon is primarily involved, at least in the terminal region of nerve fiber, in diabetic peripheral neuropathy. It is also concluded that the skin biopsy technique is harmless, cosmetically not troublesome and might be beneficial for studying peripheral neuropathies including diabetic neuropathy.

Aged↗
PubMed1984

Temperature-dependent negative cooperativity among angiotensin II receptors of isolated rat glomeruli.

The binding characteristics of angiotensin II to isolated rat glomeruli were studied at various temperatures from 15 to 37 degrees C using 125I-labeled angiotensin II. The remarkable features of the binding at 37 degrees C, compared with those at lower temperatures, were (1) decreased maximal binding due to increased dissociation rate, (2) short duration of the steady state, which was, however, sufficient for performing steady-state binding assays, and (3) marked curvilinear Scatchard plots with upward concavity. The difference between the dissociation rates caused by dilution only and by dilution plus cold angiotensin II increased with increase in temperature. From these results, we conclude that the site-site interactions of a negatively cooperative type, which are negligible at lower temperatures, exist among rat glomerular angiotensin II receptors at the physiological temperature, and that the binding study may as well be performed at 37 degrees C for the purpose of investigating quantitative correlation between the hormone binding and its biological effect.

Angiotensin II↗
PubMed1984

Prevention of peripheral nerve dysfunction by an aldose reductase inhibitor in streptozotocin-diabetic rats.

A potent inhibitor of aldose reductase, (E)-3-carboxy-methyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanin e (ONO-2235), was orally administered at a dose of 20 mg X kg-1 X d-1 for 2 weeks to streptozotocin-diabetic rats from the beginning of the diabetic state, ie, 24 hours after streptozotocin injection. The impairment of motor nerve conduction velocity (MNCV) of the tail nerve found in nontreated diabetic rats was apparently prevented by the treatment with the aldose reductase inhibitor (24.5 +/- 0.4 v 29.0 +/- 1.4 m/s on day 14, P less than 0.005). Those diabetic rats treated with the compound actually showed an age-dependent increase in MNCV similar to that of normal control rats (25.5 +/- 1.5 v 26.4 +/- 1.0 m/s on day 7, 29.0 +/- 1.4 v 29.4 +/- 1.3 m/s on day 14, treated v normal, not statistically significant on both days). The sorbitol content of the sciatic nerve excised from ONO-2235-treated diabetic rats (0.067 +/- 0.018 nmol/g wet weight) was significantly lower than that of the nontreated diabetic rats (1.309 +/- 0.080 nmol/g wet weight, P less than 0.001) but significantly higher than that of normal control rats (0.229 +/- 0.015 nmol/g wet weight, P less than 0.001). These results suggest that the reduction in MNCV noted in the experimental diabetic animals is not the result of retarded maturation of peripheral nerves but of metabolic derangement caused by the diabetic state, which can be prevented by suppressing sorbitol accumulation in nerve tissue. It also appears that there may be a threshold level of sorbitol accumulation that causes the impairment of nerve conduction velocity.

Aldehyde Reductase↗
PubMed1984

Angiotensin II effects upon glomerular intracapillary volume in the rat.

The direct action of angiotensin II on renal glomeruli was quantified by measuring extracellular space in isolated, decapsulated rat glomeruli using 14C-inulin. The glomerular inulin space significantly decreased when treated with 0.1 nM to 1 microM of angiotensin II. The decrease was dose-dependent and blocked by 1-Sar, 8-Ile angiotensin II. Since the glomerular intracapillary space seems to occupy the majority of the extracellular (inulin) space in decapsulated glomeruli, these results suggest that angiotensin Ii decreases the glomerular intracapillary volume. This action of angiotensin II may lead to a reduction in glomerular filtering surface area, and thus, in the ultrafiltration coefficient.

Angiotensin II↗
PubMed1984

Development of early lesions of microangiopathy in chronically diabetic monkeys.

A chronic diabetic state was produced in Macaca fuscatus , and these diabetic monkeys were kept without insulin treatment for up to 25 mo. The metabolic derangements were characterized by hyperglycemia, insulinopenia, hyperglucagonemia, ketonemia, and hyperlipidemia. Significant thickening of the capillary basement membrane of the gastrocnemius muscle was observed in the chronically diabetic monkeys, and became obvious in the course of diabetic state; 732 +/- 35 A in controls, 750 +/- 58 A in diabetic monkeys with duration of 4 mo, and 1165 +/- 112 A in those with duration of more than 11 mo. In addition to duration of the diabetic state, severity of hyperglycemia is also thought to play an important role in the capillary basement membrane thickening judging from the fact that diabetic monkeys with constant hyperglycemia showed a greater membrane thickening. Ultrastructural alterations, such as significant thickening of glomerular basement membrane and increase of mesangial matrix, were observed in kidney as well. These results indicate that diabetic microangiopathy has been produced by metabolic derangements characterized by chronic hyperglycemia, insulinopenia, and hyperlipidemia.

Animals↗
PubMed1984

Effects of a new aldose reductase inhibitor on various tissues in vitro.

A new aldose reductase inhibitor, ONO-2235 [(E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodanine], was found to possess a potent inhibitory activity of aldose reductase, partially purified from rat lens (IC50 = 1.0 X 10(-8) M) and human placenta (IC50 = 2.6 X 10(-8) M). Against rat lens aldose reductase, ONO-2235 exhibited uncompetitive inhibition as previously observed with 7-hydroxy-4-oxo-4H-chromen-2-carboxylic acid. Sorbitol accumulation in the isolated rat lenses, sciatic nerves and human erythrocytes were all effectively inhibited during incubation with high concentrations of glucose (28-50 mM) by ONO-2235 at a concentration of about 10(-6) M. Because the accumulation of sorbitol has been reported to play an etiological role in the development of diabetic complications, the results suggest that ONO-2235 may prove to be useful in preventing and improving some diabetic complications.

Aldehyde Reductase↗
PubMed1983

Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats.

A new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) was administered orally to streptozotocin-diabetic rats (60 mg/kg IV) for 14 days and its effect on motor nerve conduction velocity studied. The compound significantly improved motor nerve conduction velocity of diabetic rats at a minimal dose of 10 mg . kg-1 . day-1 (treated 28.8 +/- 0.5 versus untreated 23.2 +/- 4.7 m/s, p less than 0.01). The sorbitol content of the sciatic nerve and red blood cells measured after 2 weeks was concomitantly reduced in ONO-2235-treated rats (sciatic nerve: 120 +/- 13 versus 595 +/- 146 nmol/g wet weight; red blood cell: 91 +/- 21 versus 165 +/- 39 nmol/g haemoglobin; p less than 0.01 in both 20 mg . kg-1 . day-1-treated versus untreated animals). These results suggest that sorbitol accumulation might contribute to the development of peripheral nerve dysfunction in acutely diabetic animals and the new aldose reductase inhibitor could be a potential drug for therapy of diabetic neuropathy.

Aldehyde Reductase↗
PubMed1983

Insulin release from BK virus-induced and in vitro maintained insulinoma cells of Syrian golden hamster.

The pancreatic tumor cells (In 111) derived from BK virus-induced insulinoma of Syrian golden hamsters were maintained in culture for several passages and were studied for their insulin secretory ability under various stimulatory conditions. Insulin release was not increased by D-glucose stimulation (27.8 mM), while dibutyryl cyclic AMP (1 mM), theophylline (1 mM), 3-isobutyl-l-methylxanthine (0.1 mM) and elevation of medium calcium from 0.5 to 2.7 mM stimulated insulin release 2.5- to 4-fold. There was a concomitant increase of medium cyclic AMP with addition of theophylline. Streptozotocin (2 mM) treatment for 48 hours significantly reduced insulin release, while alloxan (2 mM), had no inhibitory effect on insulin release. The results indicate that while in vitro-maintained islet tumor cells, In 111, have a cyclic AMP-mediated process involved in insulin secretion analogous to normal beta cells, these cells lack the ability to recognize glucose as an insulin secretagogue probably due to a defect in the cell membrane, though the possibility of alteration in glucose metabolism cannot be fully excluded.

Adenoma, Islet Cell↗
PubMed1983

Hypokalemia and sodium retention in patients with diabetes and chronic hepatitis receiving insulin and glycyrrhizin.

Of 9 patients with chronic hepatitis treated with intravenous administration of 40 to 200 mg/day of glycyrrhizin, 3 diabetic patients receiving concomitant insulin developed hypokalemia, sodium retention and suppression of both plasma aldosterone concentration and plasma renin activity after the administration for 3 to 6 days. In the remaining 6 patients (5 nondiabetic and 1 diabetic) receiving no insulin, the administration over the long term (18 to 266 days) never caused these abnormalities. The development of hypokalemia and sodium retention in the patients was not associated with increased urinary excretion of potassium, indicating a different condition from pseudoaldosteronism caused by the desoxycorticosterone-like action of glycyrrhizin. These findings suggest that insulin which is known to have hypokalemic, antinatriuretic and antikaliuretic activity, as well as glycyrrhizin plays an important pathogenetic role in the observed electrolyte disturbance, and suppression of both renin and aldosterone.

Adult↗
PubMed1983

A community study of diabetes in a population with a high diabetes mortality rate.

Among the 47 prefectures of Japan, the prefecture of Shiga stands out due to its remarkably high death rate from diabetes, especially in female diabetics. In an attempt to clarify the causes, a diabetes detection study was carried out in the inhabitants aged 40 or over of five communities. The prevalence rate of diabetes was 1.7%; male 2.5% and female 1.3%. However, the study could include only 14% of the inhabitants (3253 out of 23,249 inhabitants). In a community named Aito, where the diabetic death rate was the highest among communities of the prefecture and the study covered 95% of the 1849 inhabitants, the prevalence of diabetes was 3.0% in males and 1.2% in females (2.2% in total). Obesity, hypertension and ischemic change in electrocardiogram were more frequent in female diabetics than in male diabetics in this community. These results suggest that the high death rate from diabetes in the female population is not caused by a high prevalence rate of diabetes and female diabetics may be affected by several risk factors which influence their prognosis more often than that of male diabetics.

Adult↗
PubMed1980

Effect of propranolol on glucose disposal rate in patients with hyperthyroidism.

The effect of propranolol treatment (60 mg per day, three days) on glucose disposal rate (K-value) was investigated in nine patients with hyperthyroidism. K-value was improved in 4 cases and aggravated in 5 cases. The fasting levels of plasma free fatty acids (FFA) before the administration of propranolol in the improved cases were significantly higher than those in the aggravated cases. The propranolol treatment markedly reduced FFA levels only in the improved cases. These results suggest that the impaired glucose tolerance frequently seen in hyperthyroidism patients could be partly attributed to the increased level of plasma FFA.

Adult↗
PubMed1978

Postbulbar duodenal ulcer occurring in a patient of diabetic coma.

Duodenal ulcer beyond the bulb occurred in a diabetic patient when he was in ketoacidotic coma causing serious anemia. Early investigation of the stomach and duodenum by endoscope was quite valuable for evaluating this bleeding complication and the healing process of the lesion was serially recorded. Since several cases of diabetic coma have been reported to die from gastrointestinal bleeding, this report presents the important aspect in the management of diabetic coma, and usefulness of emergency endoscope.

Adult↗