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Biomedical subjects

I Miwa

Publications and source records attributed to I Miwa.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cytologic characteristics of parathyroid carcinoma: a case report.

A 44-yr-old man with a preoperative diagnosis of malignant mediastinal goiter underwent a preoperative fine-needle aspiration (FNA) biopsy. Fine-needle aspiration biopsy showed enlarged uniform nuclei, prominent nucleoli, few mitotic figures, karyolysis, anuclear cells, hyalinized nonepithelial cell clusters with hemosiderin deposits, and a perivascular pseudorosette pattern. This study reviewed the current literature dealing with this cytologic feature of parathyroid carcinoma. To our knowledge, this is the first report of an oxyphilic cell type of parathyroid carcinoma detected by FNA in the English-language literature.

Adenocarcinoma↗
PubMed1998

Potentiation of glucose-induced insulin secretion by fagomine, a pseudo-sugar isolated from mulberry leaves.

The mechanisms of potentiation by fagomine, an N-containing pseudo-sugar derived from mulberry leaves, of insulin secretion from isolated rat pancreatic islets in response to glucose was studied. Fagomine at more than 1 mmol/L significantly potentiated insulin secretion induced by 10 mmol/L glucose. The pseudo-sugar, however, did not affect the basal insulin secretion assessed at a glucose concentration of 3.5 mmol/L. The effects of fagomine on 10 mmol/L and 20 mmol/L glucose-induced insulin secretion were not significantly different. Fagomine (4 mmol/L) also potentiated glyceraldehyde-induced insulin secretion, but not the leucine-induced type. Glycolysis assessed by lactate production from glucose was significantly enhanced. The amounts of all intermediates (from glucose 6-phosphate to glyceraldehyde 3-phosphate) of the upper part of the glycolytic pathway in islets incubated with 20 mmol/L glucose were not affected by 4 mmol/L fagomine. The rise in the ATP/ADP ratio through both the glycolytic pathway and the citric acid cycle is believed to be pivotal in glucose- and glyceraldehyde-induced insulin secretion; whereas the ATP/ADP ratio rise through the citric acid cycle via the formation of acetyl-CoA is involved in leucine-induced insulin secretion. Our findings, together with these considerations, suggest that fagomine potentiates glucose-induced insulin secretion through acceleration of some step(s) after the formation of glyceraldehyde 3-phosphate in the glycolytic pathway.

Acetyl Coenzyme A↗
PubMed1997

Glucokinase is located in secretory granules of pancreatic D-cells.

We immunohistochemically examined the distribution of glucokinase in rat pancreatic islets. Glucokinase immunoreactivity under light microscopy was detected in the cytoplasm of somatostatin cells as well as in that of insulin cells. No specific immunoreactivity was detected in glucagon and pancreatic polypeptide cells. In somatostatin cells, glucokinase immunoreactivity was located by electron microscopy exclusively within secretory granules.

Animals↗
PubMed1997

Co-localization of glucokinase with actin filaments.

A portion of glucokinase appeared to be co-localized with actin filaments in the cytoplasm of cultured rat hepatocytes incubated with 25 mM glucose. When liver- or islet-type glucokinase was transiently expressed in COS-7 cells, the expressed glucokinase was also co-localized with actin filaments in the cytoplasm of these transfected cells. Although co-localization of glucokinase with actin filaments was not clearly demonstrated in the pancreatic beta-cell line MIN6, islet glucokinase was found to be present in both the nucleus and the cytoplasm, though predominantly in the nucleus. These findings suggest that subcellular localization of glucokinase, including co-localization with actin filaments, may have an important physiological role in metabolic regulation.

Actins↗
PubMed1997

Stimulatory effect of fatty acid treatment on glucose utilization in human erythrocytes.

We previously reported that treatment of human erythrocytes with bee venom phospholipase A2 increased the rate of lactate production from glucose. This increase was suggested to be mediated through liberation of free fatty acids from membrane phospholipids. So, in the present study we examined the mechanism of stimulation of glycolysis by fatty acids. Treatment of intact erythrocytes with most of the 15 fatty acids tested resulted in stimulation of lactate production from glucose. Among the fatty acids tested, myristoleic acid showed the highest stimulatory activity. The ratio of moles of lactate produced to those of glucose utilized was about 1.9 in both myristoleic acid-treated and untreated cells. Treatment of erythrocytes with myristoleic acid did not affect the amount of 2,3-bisphosphoglycerate. Lactate production from D-glyceraldehyde, which is thought to be phosphorylated to D-glyceraldehyde 3-phosphate and then metabolized in the glycolytic pathway, was not at all affected by treatment of cells with myristoleic acid. The cross-over plot of glycolytic intermediates suggested that the enhancement of glycolysis was induced by activation of the 6-phosphofructokinase (PFK) step. Fatty acids incorporated into erythrocytes were found to be present predominantly in the cytoplasm rather than in the plasma membrane. The PFK activity, but not the hexokinase activity, in hemolysates was clearly increased by a set of fatty acids, and myristoleic acid was again the most potent. However, partially purified human erythrocyte PFK was not activated by the acid. We conclude that fatty acids stimulate glycolysis through activation of PFK in cooperation with some other component(s) in erythrocytes.

Enzyme Activation↗
PubMed1997

4-Hydroxy-2-nonenal hardly affects glycolysis.

4-Hydroxy-2-nonenal (HNE), one of the major products of lipid peroxidation, inactivated the rate-limiting enzymes (from animal sources) of the glycolytic pathway and the pentose phosphate pathway when incubated at 37 degrees C for 1 h in the absence of glutathione (GSH). The HNE concentration for half-maximal inactivation of 6-phosphofructokinase (PFK) and glyceraldehyde-3-phosphate dehydrogenase was 3-10 microM; and that value for pyruvate kinase, glucose-6-phosphate dehydrogenase, and hexokinases I and II was 0.15-0.6 mM. In the presence of 5 mM GSH, however, only PFK, irrespective of the source (muscle, liver, or erythrocyte), was inactivated by 40-50% when incubated with 0.1 mM HNE for 1 h. Even PFK was not inactivated in the presence of both GSH and its substrate, ATP (2 mM). Glycolysis in human erythrocytes was not affected by treatment of cells with 0.1 mM HNE at 37 degrees C for 30 min. The results suggest that HNE, at concentrations observable under physiological and pathological conditions, hardly affects glycolysis in cells.

Aldehydes↗
PubMed1997

Molecular cloning and nucleotide sequence of the arginase gene of Bacillus brevis TT02-8 and its expression in Escherichia coli.

The gene from Bacillus brevis TT02-8 encoding arginase was cloned into Escherichia coli, and its nucleotide sequence was identified. The nucleotide sequence contained an open reading frame that encoded a polypeptide of 298 amino acid residues with a predicted molecular weight of 31,891, which was consistent with that previously calculated for arginase purified from this bacterium. Comparison of the deduced amino acid sequence of the B. brevis TT02-8 arginase with that of the prokaryotic and eukaryotic arginases of Bacillus caldovelox, Bacillus subtilis, Agrobacterium Ti plasmid C58, Saccharomyces cerevisiae, Coccidioides immitis, Xenopus laevis, Rana catesbeiana, rat liver, and human liver, showed 33-66% of the sequences to be similar; there were several highly conserved regions. Arginase activity was detected in Escherichia coli cells transformed with an expression plasmid of the cloned arginase gene.

Amino Acid Sequence↗
PubMed1997

Shuttling of glucokinase between the nucleus and the cytoplasm in primary cultures of rat hepatocytes: possible involvement in the regulation of the glucose metabolism.

Glucokinase (GK) is believed to play a key role in the control of the hepatic glucose metabolism. To address the mechanism of the regulation of glucose metabolism through GK action, we immunohistochemically studied changes in GK distribution in primary cultures of rat hepatocytes. In hepatocyte monolayers incubated in 5 mM glucose, GK staining by the immunoperoxidase method was observed predominantly in the nucleus. When cultured hepatocytes were incubated for 30 min in various concentrations (5-45 mM) of glucose, there was an appreciable decrease in nuclear GK immunoreactivity, even at 10 mM compared with that at 5 mM. After the shift of glucose concentration from 5 mM to 25 mM, the GK distribution changed time-dependently over 1 h. A time-dependent change in GK distribution was also observed when the glucose concentration was shifted from 25 mM to 5 mM. Reversal of GK distribution in response to the change in glucose concentration from 5 to 25 mM and vice versa was shown to repeatedly occur. Lower concentrations (0.05-5 mM) of fructose, which is known to stimulate glucose phosphorylation by GK, in combination with 5 mM glucose, induced the translocation of GK from the nucleus to the cytoplasm. Mannose (20 mM), a substrate of GK, and sorbitol (1 mM), a stimulator of glucose phosphorylation by GK, induced the translocation of GK from the nucleus to the cytoplasm in the presence of 5 mM glucose. L-glucose, galactose, 3-O-methylglucose, and 2-deoxyglucose at 20 mM each did not affect the GK distribution observed in the presence of 5 mM glucose. The results suggest that GK is present mainly in the nucleus under conditions where GK action is not much needed, whereas the enzyme exists mainly in the cytoplasm under conditions where it must function extensively. Our findings indicate that the shuttling of GK between the nucleus and the cytoplasm is essential for the regulation of the glucose metabolism in the liver.

Animals↗
PubMed1997

Effects of 1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin on human aldose reductase examined by a new application of HPLC system for measuring tissue polyol.

M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin, CAS 128851-36-5) displayed potent inhibitory effects upon recombinant human aldose reductase (rhAR, IC50 = 0.051 mumol/l). The inhibition of rhAR by M16209 was uncompetitive with respect to both glyceraldehyde and NADPH. The effects of M16209 on human AR were investigated using a new application of HPLC system developed for analysis of tissue polyol. M16209 and epalrestat suppressed galactitol accumulation in human erythrocytes cultured in 25 mmol/l galactose with IC50 values of 1.2 and 2.6 mumol/l, respectively. The new application of HPLC system equipped with an electrochemical detector did not require any derivatization procedure for polyols and enabled simultaneous determination of glucose, galactose, fructose, myo-inositol, galactitol and sorbitol.

Aldehyde Reductase↗
PubMed1996

Amelioration of insulin resistance in genetically obese rodents by M16209, a new antidiabetic agent.

Improvement of metabolic disorders by M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent, was studied in genetically obese Zucker fa/fa rats and C57BL/6J ob/ob mice. In fa/fa rats oral administration of M16209 (30 and 100 mg/kg/day) for 7 days dose dependently improved hyperinsulinemia without affecting body weight. Oral glucose loading (2 g glucose/kg body weight) after 10 days of administration to fa/fa rats revealed that M16209 significantly improved glucose tolerance both 30 and 60 min after glucose loading, but did not affect preload serum glucose levels. At one day after 13 days of administration of M16209, the serum levels of triglyceride, total cholesterol and free fatty acid were clearly lower in treated fa/fa rats than those in untreated rats. In C57BL/6J ob/ob mice, M16209 given for 28 days at doses of 30 and 100 mg/kg/day improved hyperinsulinemia, hyperglycemia and hypercholesterolemia without affecting body weight. In a hyperinsulinemic euglycemic clamp study in fa/fa rats, administration of M16209 for 7 days at a dose of 100 mg/kg/day significantly normalized the decreased metabolic clearance rate but did not show any effect on the augmented hepatic glucose output. These findings demonstrate that improvement of metabolic disorders in genetically obese rodents by M16209 is due to amelioration of insulin resistance in peripheral tissues.

Administration, Oral↗
PubMed1996

Effects of M16209, a new antihyperglycemic agent, on insulin sensitivity in vivo: euglycemic clamp studies in rats.

The effects of M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) on the in vivo insulin sensitivity of rats were studied by euglycemic clamp methods after 1 week of administration (10 or 100 mg/kg/d). M16209 increased both the glucose infusion rate (GIR) and metabolic clearance rate (MCR) of 3-[3H]-glucose, but did not suppress hepatic glucose output. M16209 also increased the [3H]-2-deoxyglucose utilization rate, rate of incorporation of [14C]-glucose into glycogen, and glycolytic flux in the soleus and red gastrocnemius muscles, but not in the extensor digitorum lungus and white gastrocnemius muscles. M16209 affected neither the [3H]-2-deoxyglucose utilization rate nor the rate of incorporation of [14C]-glucose into lipids in epididymal adipose tissue. In the soleus muscle, M16209 decreased glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) content, but did not affect fructose-1,6-bisphosphate (F-1,6-BP) content. Moreover, M16209 increased glycogen synthase-I activity and fructose-2,6-bisphosphate (F-2,6-BP) content in the soleus muscle. These results suggest that M16209 increases insulin-stimulated glucose uptake in peripheral tissues, particularly oxidative muscles, through potentiation of insulin action on glycogen synthesis and glycolysis. Glycogen synthase and phosphofructokinase (PFK) appear to be major targets of the action of M16209.

Adult↗
PubMed1996

Inhibition of advanced protein glycation by 8-quinolinecarboxylic hydrazide.

Glycation of proteins is belived to be involved in the pathogenesis of diabetic complications, and thus the development of potent inhibitors of protein glycation is highly desirable. We tested the inhibitory effects of 12 hydrazide compounds against protein glycation and compared them with the effects of aminoguanidine (AG), a well-known inhibitor. When bovine serum albumin (BSA) was incubated with 100 mmol/l mannose for 10 days at 37 degrees C in the presence and absence of hydrazide compounds or AG at 1 mmol/l, only p-anisic hydrazide inhibited Amadori product formation. On the other hand, 8 hydrazides as well as AG inhibited the formation of advanced glycation end products (AGEs). 8-Quinolinecarboxylic hydrazide (8-QCH), the most potent hydrazide, was more effective than AG. Neither 8-QCH nor AG affected the spontaneous decrease in Amadori products of preglycated BSA in the absence of sugar, but suppressed the spontaneous increase in AGEs from preglycated BSA, with higher potency of 8-QCH relative to AG. The results indicate that 8-QCH is a more potent inhibitor of AGE formation than AG and suggest that the inhibition mechanisms of 8-QCH and AG resemble each other.

Glycoproteins↗
PubMed1996

Acceleration of glycolysis in erythrocytes by the antidiabetic agent M16209.

The effects of M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent and aldose reductase inhibitor, on glycolysis were studied in rat and human erythrocytes in vitro. M16209 increased lactate production from glucose when incubated with rat and human erythrocytes, and also increased glucose consumption in rat erythrocytes. The rates of production of lactate in rat erythrocytes treated with M16209 at 10, 25 and 50 microM were 113, 118 and 123%, respectively, of those in vehicle treated cells. Sorbinil (aldose reductase inhibitor), tolbutamide (sulfonylurea), and buformine (biguanide) did not increase lactate production in rat erythrocytes when tested at 50 microM. On the other hand, M16209 did not affect lactate production from D-glyceraldehyde in rat erythrocytes. At 100 microM the agent decreased both glucose-6-phosphate and fructose-6-phosphate in rat erythrocytes, and increased fructose-1,6-bisphosphate; at 10 microM it also increased 6-phosphofructokinase activity in rat hemolysates. These findings suggest that M16209 accelerates glycolysis in erythrocytes via activation of 6-phosphofructokinase.

Aldehyde Reductase↗
PubMed1995

Nuclear location of the regulatory protein of glucokinase in rat liver and translocation of the regulator to the cytoplasm in response to high glucose.

Rat liver is known to contain a regulatory protein (RP) that inhibits glucokinase competitively with respect to glucose. By an immunohistochemical technique and by cell fractionation in glycerol, we investigated the distribution of RP in rat liver and its changes in response to high glucose. RP was detected almost exclusively in the nuclei of the parenchymal cells of both fed and fasted rats. In situ perfusion of the liver with 20 mM glucose for 10 min caused a marked decrease in nuclear RP and an increase in cytoplasmic RP. These results indicate that RP is present predominantly in the nuclei of hepatocytes and is translocated from the nucleus to the cytoplasm in response to high glucose.

Animals↗
PubMed1995

Antihyperglycemic effects of M16209, a novel aldose reductase inhibitor, in normal and diabetic rats.

The effect of a single oral administration of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on serum glucose was investigated. In normal rats, M16209 (100 mg/kg) had a weak hypoglycemic effect but markedly stimulated the disappearance of serum glucose in intravenous glucose tolerance tests. In diabetic rats, M16209 (100 mg/kg) significantly suppressed the hyperglycemia of streptozotocin-induced, mildly diabetic rats and stimulated serum glucose disappearance in neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM) rats in glucose tolerance tests. Additionally, M16209 augmented insulin secretion in glucose-loaded, normal and NIDDM rats and restored the reduced serum insulin in streptozotocin-induced, mildly diabetic rats. M16209, however, showed no hypoglycemic effect in severely diabetic rats. In contrast, gliclazide, a sulfonylurea, showed a much more potent hypoglycemic effect in normal rats than in mildly diabetic rats. These results suggest that M16209 suppresses hypoglycemia through augmentation of glucose-stimulated insulin secretion. The antihyperglycemic activity of M16209, combined with its potent aldose reductase inhibiting activity, is expected to be beneficial in the treatment of diabetic complications.

Aldehyde Reductase↗
PubMed1995

Effects of M16209 on insulin secretion in isolated, perfused pancreases of normal and diabetic rats.

We investigated the stimulatory effect of M16209 (1-(3-bromobenzo[b]furan-2-yl-sulfonyl)hydantoin), a novel aldose reductase inhibitor, on insulin secretion using isolated, perfused pancreases of rats. In the pancreases from normal rats, M16209 (100 microM) greatly augmented glucose-stimulated insulin secretion, but showed no effect on unstimulated insulin secretion at 2.8 mM glucose. In contrast, gliclazide (10 microM), a sulfonylurea, strongly enhanced both glucose-stimulated and unstimulated insulin secretion. Sorbinil and epalrestat, potent aldose reductase inhibitors, had no stimulatory effect on insulin secretion. M16209 (100 microM) improved appreciably the decreased insulin response to 22.2 mM glucose and enhanced slightly unstimulated insulin secretion in the pancreases of rats with neonatally streptozotocin-induced, non-insulin-dependent diabetes mellitus (NIDDM). Gliclazide (10 microM), however, failed to affect the pancreases of NIDDM rats. Furthermore, M16209 showed no appreciable effect on ATP-sensitive K(+)-channels in pancreatic beta-cells. These results suggest that M16209, unlike sulfonylureas, selectively enhances glucose-stimulated insulin secretion in both normal and NIDDM rats through a direct action on the pancreas. The site of action remains unknown, but the inhibition of aldose reductase or the ATP-sensitive K+ channels is unlikely to be involved.

Aldehyde Reductase↗
PubMed1995

Changes in subcellular and zonal distribution of glucokinase in rat liver during postnatal development.

Subcellular and zonal distribution of glucokinase in rat liver during postnatal development was examined immunohistochemically. Before day 11 after birth, only some hepatocytes were immunostained, and a positive immunostaining was found in the cytoplasm but not in the nucleus. No zonal distribution of glucokinase was observed in livers of such pups. From day 15, at which time a dietary change from milk to laboratory chow begins to take place, glucokinase immunoreactivity increased; this increase was associated with increases in glucokinase activity and in glucokinase protein, and also the immunostaining was observed mainly in the nuclei. At day 21, the glucokinase immunoreactivity was found almost exclusively in the perivenous zone. At day 30, an intense immunostaining was seen both in the perivenous zone and in the periportal zone, being slightly predominant in the former. The present results indicate that dramatic changes in the distribution of glucokinase in developing rat liver may be related to dietary change.

Aging↗