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Biomedical subjects

F Horio

Publications and source records attributed to F Horio.

At least 19 recordsLinked to original sources
PubMed2006

Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic SMXA-5 mouse established from non-diabetic SM/J and A/J strains.

AIMS/HYPOTHESIS: The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat diet. The aim of this study was to dissect the diabetogenic loci in the A/J regions of the SMXA-5 genome that contribute to diabetes-related traits. MATERIALS AND METHODS: We analysed the quantitative trait loci (QTL) for diabetes-related traits and obesity in (SM/JxSMXA-5)F(2) intercross mice fed a high-fat diet. To verify the function of the responsible locus that was mapped in the present study, we constructed a congenic strain and characterised its diabetes-related traits. RESULTS: A major QTL for glucose tolerance, free-fed blood glucose concentration and BMI was mapped on chromosome 2. This locus existed near D2Mit15, with the highest logarithm of the odds score (12.6) for glucose concentration at 120 min in a glucose tolerance test, and was designated T2dm2sa. The diabetogenic allele of T2dm2sa originated in the A/J strain. SM.A-T2dm2sa, a congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J, exhibited overt impaired glucose tolerance and hyperinsulinaemia. CONCLUSIONS/INTERPRETATION: The development of impaired glucose tolerance in SM.A-T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in F(2) intercross mice. The present results suggest that there are latent diabetogenic loci in the genomes of non-diabetic A/J and SM/J mice, and that the coexistence of these loci, including T2dm2sa, causes impaired glucose tolerance in SMXA-5 and SM.A-T2dm2sa mice.

Animals↗
PubMed2001

A newly established strain of spontaneously hypertensive rat with a defect of ascorbic acid biosynthesis.

To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.

Aging↗
PubMed2001

Quantitative trait loci for body weight in the intercross between SM/J and A/J mice.

We performed a genome-wide quantitative trait locus (QTL) analysis of body weight at 10 weeks of age in a population of 321 intercross offspring from SM/J and A/J mice, progenitor strains of SMXA recombinant inbred strains. Interval mapping revealed two significant QTLs, Bwq3 (body weight QTL3) and Bwq4, on Chromosomes (Chrs) 8 and 18 respectively, and five suggestive QTLs on Chrs 2, 6, 7, 15 and 19. Bwq3 and Bwq4 explained 6% of the phenotypic variance. The SM/J alleles at both QTLs increased body weight, though the SM/J mouse was smaller than the A/J mouse. On the other hand, four of the five suggestive QTLs detected had male-specific effects on body weight and the remainder was female-specific. These suggestive QTLs explained 5-6% of the phenotypic variance and all the SM/J alleles decreased body weight.

Alleles↗
PubMed2001

Blood and liver lipid concentrations in EDS shrews exhibiting spontaneous non-insulin dependent diabetes mellitus (NIDDM).

The EDS (early-onset diabetes in suncus) colony was developed as a new laboratory colony of the musk shrew and is characterized by a high incidence of early-onset spontaneous non-insulin dependent diabetes mellitus (NIDDM). We examined blood lipid (triglyceride [TG], total cholesterol [TC], phospholipid [PL], free fatty acid [FFA]) and liver lipid (TG, TC, PL) concentrations to investigate the features of lipid metabolism in these animals. All lipid concentrations examined both in blood and liver of the diabetic shrews had a tendency toward higher values than those in non-diabetic shrews. The PL concentration was the only parameter that barely showed a significant difference. Values for all blood lipid concentrations in diabetic shrews at 7-9 months tended to be higher than those of 2-month-old diabetic shrews, although the difference was not significant. These findings indicate that diabetic EDS shrews exhibit a much milder defect of lipid metabolism induced by NIDDM than other rodent models.

Animals↗
PubMed2000

Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, Wasabi.

6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of an another screening for the induction of glutathione S-transferase (GST) activity in RL34 cells, MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its high reactivity with sulfhydryl (RSH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

Animals↗
PubMed2000

The role of anthocyanins as an antioxidant under oxidative stress in rats.

Cyanidin 3-O-beta-D-glucoside (C3G) is included in anthocyanins, and expected to have a potency to scavenge active oxygen species in vivo. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days, and then subjected to hepatic ischemia-reperfusion (I/R) as an oxidative stress model. I/R treatment elevated the liver thiobarbituric acid-reactive substance concentration and the serum activities of marker enzymes for liver injury, and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. These results indicate that C3G functions as a potent antioxidant in vivo under oxidative stress. To clarify the mechanism of action of C3G, we investigated the absorption and metabolism of C3G in rats. C3G appeared in the plasma immediately after the oral administration of C3G. Protocatechuic acid, which seems to be produced by the degradation of cyanidin, was also present in the plasma. In the liver and kidneys, C3G was metabolized to methylated form.

Animals↗
PubMed2000

Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, wasabi.

6-Methylsulfinylhexyl isothiocyanate (MS-ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of another screening for the induction of glutathione S-transferase (GST) activity in RL34 cells. MS-ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS-ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS-ITC, the isothiocyanate moiety of MS-ITC plays an important role for antiplatelet and anticancer activities because of its highly reactivity with sulfhydryl (-SH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).

Antineoplastic Agents, Phytogenic↗
PubMed2000

Fatty liver and hyperlipidemia in IDDM (insulin-dependent diabetes mellitus) of streptozotocin-treated shrews.

Severe IDDM (insulin-dependent diabetes mellitus) was produced in the musk shrew (Suncus murimus, Insectivora) by a high dose (a single intraperitoneal injection of 100 mg/kg Body Weight) of streptozotocin (STZ) injection. All shrews that were administered a high dose of STZ exhibited hyperglycemia (449 +/- 16 mg/dl vs 73 +/- 4 mg/dl in controls) and hypoinsulinemia(0.25 +/- 0.07 ng/ml vs 10.96 +/- 1.97 ng/ml in controls) with ketosuria 10 days after injection. Their livers were enlarged and exhibited ayellowish-brown color with marked triglyceride (TG) accumulation (63.25 +/- 7.10 mg/g Liver vs 2.11 +/- 0.19 mg/g Liver in controls). It is probable that the increased influx of fatty acids into the liver induced by hypoinsulinemia and the low capacity of excretion of lipoprotein secretion from liver in the musk shrew resulting from a deficiency of apolipoprotein B synthesis play important roles in fatty liver formation. Hyperlipidemia was another feature in shrews with severe IDDM. The blood TG level was especially high in these shrews (899 +/- 178 mg/dl vs 23 +/- 5 mg/dl in controls). These results indicate that the IDDM shrew, induced by high doses of STZ, is a unique model characterized by fatty liver and hyperlipidemia and may be useful for studying lipid metabolism of IDDM.

Animals↗
PubMed2000

Increase in production of ascorbate radical in tissues of rat treated with paraquat.

The production of ascorbate radical (A*-) was investigated in tissues of rats intoxicated with paraquat (PQ) to know the protective role of antioxidant ascorbate (AH-) in tissues. The electron spin resonance (ESR) method is applied to observe A*-. To eliminate increased biosynthesis of ascorbic acid (AH2) by PQ intoxication, ODS rats were chosen and fed with or without 250 ppm PQ in the diet. The radical A*- was detected only in the lung and spleen homogenates of both intoxicated and control rats at the beginning of ESR measurement. The radical levels of intoxicated rat lung and spleen were increased rapidly to twice the initial level after 3 h and decreased to 0.2-0.6 times the initial level after 24 h, whereas those of control rats were increased slowly to 1.1 times the initial level after 4 h and decreased slowly to 0.7 times the initial level after 24 h at 4 degrees C. In other organs such as liver, kidney, heart and testis, A*- was not detected initially but detected afterwards. Higher A*- level was observed in the intoxicated rat liver than the control but no appreciable differences of A*- levels were observed between the intoxicated kidney, heart and testis and the respective controls. In the intoxicated rat lung the concentration of AH2 is only half but that of A*- is twice as high as that of the control. Larger amounts of A*- produced in the intoxicated rats decayed more quickly than those in the control rats. The simple addition of PQ to the control organ enhanced neither A*- production nor A*- quenching. These facts suggest that the tissues damaged by PQ require larger amounts of AH- to detoxicate harmful oxidants, resulting in concomitant production of A*-.

Animals↗
PubMed2000

Developing a new model for non-insulin dependent diabetes mellitus (NIDDM) by using the Philippine wild mouse, Mus musculus castaneus.

The Philippine wild-caught castaneus mouse (Mus musculus castaneus) and laboratory mouse (C57BL/6J: B6) were used to develop a new non-insulin dependent diabetes mellitus (NIDDM) model. Offspring from the cross between a wild male and B6 female were backcrossed to the sire. One male which exhibited highest fasting hyperglycemia (190 mg/dl) among eighty-seven backcross offspring was selected at 10 weeks of age, and crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed to develop a new inbred strain named CBD (Castaneus-B6 diabetic) mouse. Mice with relatively higher fasting hyperglycemia among F0 and F1 generations were selected for breeding. From the F2 generation, mice were defined as diabetic when blood glucose levels exceeded 200 mg/dl at 120 min in intraperitoneal glucose tolerance test (IPGTT) at 10 weeks of age, and have been selectively bred. The incidence of diabetic males from the F3-F6 generation fluctuated 45-75% at 10 weeks of age and 59-72% at 20 weeks of age. Diabetic males had about two-fold higher fasting glucose and insulin levels than B6 males. Glucose-stimulated insulin secretion was impaired in diabetic CBD mice compared to B6 males at 20 weeks. Moreover, diabetic mice had slight obesity compared to B6 mice. These facts indicated that diabetic features of CBD mice resemble NIDDM in humans. The CBD strain, characterized by high incidence and early onset of diabetes with mild obesity would be of value as a new NIDDM model. The method, utilizing wild castaneus mouse of different origin from laboratory mice, maybe useful in the development of other animal models.

Animals↗
PubMed2000

Distribution of body weight, blood insulin and lipid levels in the SMXA recombinant inbred strains and the QTL analysis.

In the SMXA recombinant inbred (RI) strains, we measured body weight, blood insulin and lipid (triglyceride, total cholesterol and phospholipid) levels in each strain. In the five traits, mean values of substrains varied remarkably and showed a continuous spectrum of distribution, suggesting control by multiple genes at distinct loci for each trait. We also screened for quantitative trait loci (QTLs) involved in the five traits. Suggestive QTLs for body weight (Chromosomes 1 and 6), insulin (Chromosomes 1, 3, 10 and 17), triglyceride (Chromosomes 4 and 11) and phospholipid (Chromosome 18) levels were detected. The SMXA RI strains are unique tools for analyzing genetic factors that influence body weight, blood insulin and lipids levels.

Animals↗
PubMed2000

Characterization of hyperinsulinemic recombinant inbred (RI) strains (SMXA-5 and SMXA-9) derived from normoinsulinemic SM/J and A/J mice.

We discovered two mouse strains (SMXA-5 and SMXA-9) with hyperinsulinemia among the substrains and progenitor strains (SM/J and A/J) of the SMXA recombinant inbred (RI) strains, and characterized the two strains at 20 weeks of age. SMXA-5 (mean +/- S.E.M: 9.6 +/- 1.7 ng/ml) and SMXA-9 (7.7 +/- 1.3 ng/ml) males had higher serum immunoreactive insulin levels than SM/J (1.4 +/- 0.3 ng/ml) and A/J (1.1 +/- 0.1 ng/ml) males in the nonfasting condition. The hypoglycemic response to insulin at 30 min after injection was significantly less in SMXA-5 males than in SM/J mice. Glucose tolerance test revealed that the incidence of impaired glucose tolerant males was 58% (11/19) in SMXA-5 and 42% (10/24) in SMXA-9 strains, but none in SM/J and A/J strains. SMXA-5 (209 +/- 29 mg/dl) and SMXA-9 (235 +/- 31 mg/dl) had higher serum triglyceride levels than SM/J (126 +/- 14 mg/dl) and A/J (89 +/- 5 mg/dl) males in the nonfasting condition. Histologic examination revealed enlarged islets in the pancreas of hyperinsulinemic SMXA-5 male mice. Moreover, SMXA-5 and SMXA-9 mice exhibited mild obesity. SMXA-5 and SMXA-9 males were therefore characterized by hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and mild obesity which resembled some of the phenotypes of human Syndrome X, although both progenitor strains were normal so far as we examined. Since the RI strains are a powerful tool to facilitate polygenic-trait analysis, SMXA-5 and SMXA-9 mice will be useful materials to investigate the genetic basis of complex diseases, and are possible new metabolic models in relation to hyperinsulinemia.

Animals↗
PubMed1999

Protective effects of dietary cyanidin 3-O-beta-D-glucoside on liver ischemia-reperfusion injury in rats.

We recently reported that feeding cyanidin 3-O-beta-d-glucoside (C3G), a typical anthocyanin pigment, lowered the serum thiobarbituric acid-reactive substance (TBARS) concentration and increased the oxidation resistance of the serum to lipid peroxidation in rats. These results suggest that C3G acts as a potent antioxidant in vivo when acute oxidative stress is encountered. In the present study, we evaluated whether feeding C3G suppresses oxidative injury to the liver caused by hepatic ischemia-reperfusion (I/R), which was used as a model for oxidative stress. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days and then subjected to hepatic I/R. I/R treatment elevated the liver TBARS concentration and the serum activities of marker enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase) for liver injury and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. Although the liver ascorbic acid concentration was also lowered by hepatic I/R, feeding C3G restored this concentration more quickly compared to the control rats. These results indicate that orally administered C3G suppresses I/R-induced oxidative damage and suggest that C3G functions as a potent antioxidant in vivo under oxidative stress.

Animals↗
PubMed1999

Absorption and metabolism of cyanidin 3-O-beta-D-glucoside in rats.

We have clarified for the first time how cyanidin 3-O-beta-D-glucoside (C3G), which is a potent antioxidant anthocyanin, is absorbed and metabolized in vivo. Rats were orally administered C3G (0.9 mmol/kg body weight), and C3G rapidly appeared in the plasma. However, the aglycon of C3G (cyanidin; Cy) was not detected, although it was present in the jejunum. Protocatechuic acid (PC), which may be produced by degradation of Cy, was present in the plasma and the concentration was 8-fold higher than that of C3G. These results suggest that plasma PC and C3G may contribute to the antioxidant activity of the plasma. In the liver and kidney, C3G was metabolized to methylated C3G (methyl-C3G), suggesting that C3G and/or methyl-C3G act as antioxidants in the tissues.

Absorption↗
PubMed1998

Dietary cyanidin 3-O-beta-D-glucoside increases ex vivo oxidation resistance of serum in rats.

The effect of dietary cyanidin 3-O-beta-D-glucoside (C3G), a typical anthocyanin pigment, on the generation of thiobarbituric acid reactive substances (TBARS) during serum formation ex vivo and susceptibility of serum to further lipid peroxidation was studied in rats. Rats were fed a diet containing C3G (2 g/kg) for 14 d. Feeding C3G resulted in a significant decrease in generation of TBARS during serum formation. The serum from the C3G-fed group showed a significantly lower susceptibility to further lipid peroxidation provoked by 2,2'-azobis(2-amidinopropane)hydrochloride or Cu2+ than that of the control group. No significant differences were observed in serum phospholipid, triglyceride, esterified cholesterol, and free fatty acid concentrations between the control and the C3G-fed groups. Concentrations of endogenous antioxidants remaining in the serum after blood coagulation were not affected by the C3G feeding. These results demonstrate that feeding C3G increases the ex vivo oxidation resistance of the serum without affecting serum endogenous antioxidant levels, and reduces the TBARS generated during serum formation without changing the concentrations of serum lipids.

Amidines↗
PubMed1998

Toxin-induced IDDM (insulin dependent diabetes mellitus) in the musk shrew.

We administered streptozotocin (STZ) and alloxan (AL) to the musk shrew (Suncus murinus, Insectivora) to determine the effective diabetogenic dose of the two toxins for this species. A single intraperitoneal (i.p.) injection of 75 mg/kgBW or the consecutive 5-day s injection of 25 mg/kgBW of STZ to non-fasted shrews, effectively (100%) induced hyperglycemia (> or = 300 mg/dl) with hypoinsulinaemia (< 30% of control level) in male shrews at 10 days after administration. Morphological studies showed cytological changes of B cells in the pancreatic islets of diabetic shrews. Hyperglycemic shrews induced by STZ were thus in IDDM (insulin dependent diabetes mellitus), and showed high susceptibility to the diabetogenic effect of STZ as compared with rodents. Shrews showed a sex difference in the diabetogenic susceptibility to STZ as do mice (male > female). They also showed a species specific resistance to the diabetogenic effect of AL. Of the eight shrews (with 8-hr fasting) that has been treated with a single injection of 200 mg/kgBW of AL, seven (88%) survived at least 10 days, showing no signs of hyperglycemia. All shrews died within 3 day s after injection of 250 or 300 mg/kgBW. These results indicated that the STZ-induced diabetic shrew is a unique animal model and may be useful for IDDM research. On the other hand, the musk shrew was highly resistant to the diabetogenic effects of AL.

Alloxan↗
PubMed1998

Ascorbic acid deficiency changes hepatic gene expression of acute phase proteins in scurvy-prone ODS rats.

The ODS rat (genotype od/od), which has a hereditary defect in ascorbic acid biosynthesis, was used to investigate the effects of ascorbic acid deficiency on the hepatic gene expression of both the positive acute phase proteins, haptoglobin and alpha1-acid glycoprotein, and the negative acute phase proteins, apolipoprotein A-I and albumin. Male ODS rats (6 wk old, body weight approximately 140 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 d. Ascorbic acid deficiency significantly elevated the serum concentration of haptoglobin and significantly lowered those of apolipoprotein A-I and albumin. The hepatic mRNA levels of haptoglobin and alpha1-acid glycoprotein in the ascorbic acid-deficient rats were significantly elevated on d 12, and reached 260 (P < 0.05) and 360% (P < 0.01) of respective values in the control rats on d 14. On the contrary, the hepatic mRNA levels of apolipoprotein A-I and albumin in the ascorbic acid-deficient rats were lowered to 68 (P < 0.01) and 71% (P < 0.05) of respective values in the control rats on d 14. Although ascorbic acid deficiency significantly elevated the serum corticosterone concentration on d 14, the changes in mRNA levels of haptoglobin, alpha1-acid glycoprotein, apolipoprotein A-I and albumin due to ascorbic acid deficiency were not affected by adrenalectomy, as assessed in a separate experiment. The serum concentration of interleukin-6, an inflammatory cytokine that stimulates gene expression of some acute phase proteins, was significantly higher in the ascorbic acid-deficient rats on d 14 than in the control rats. These results suggest that ascorbic acid deficiency causes physiologic changes similar to those that occur in the acute phase response.

Acute-Phase Proteins↗