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1.
Lab Anim Res ; 38(1): 20, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-35851065

ABSTRACT

BACKGROUND: Gastrointestinal microbiota, which comprises hundreds of different types of microbes, biologically plays crucial roles in the host's health. Probiotics (PRO) did not always have a positive benefit on the host, depending on strains of microbes and the physiochemical properties of prebiotics (PRE), indicating that the properties of PRE in combination with PRO might have different effects on the gut ecology. The aim of this study was to assess the effects of insoluble or soluble PRE with PRO on intestinal digestive hydrolase, the fecal microbes, and immunological biomarkers in SD rats fed an AIN-93G diet. RESULTS: Forty, 8-week-old SD rats were randomly assigned to 4 groups with 10 replicates in each; cellulose (CELL), cellulose + probiotics (CELPRO), oatmeal (OATS), and oatmeal + probiotics (OATPRO) groups. After 4-week feeding trial, rats were treated with saline or lipopolysaccharide (LPS, 1 mg/kg) to examine the alleviating effects of PRO and PRE on immunological responses. There was a significant (p < 0.05) decrease in feed intake of rats fed the oatmeal supplemented diet without affecting growth performance. Blood triglyceride was significantly (p < 0.05) decreased in rats fed the oatmeal diet, and aspartate aminotransferase (AST) was significantly (p < 0.05) decreased in rats fed the PRO supplemented diet. Intestinal maltase, sucrose, and lactase activities were significantly (p < 0.05) higher in rats fed PRO compared with rats not fed PRO. Rats fed the oatmeal showed a significant (p < 0.01) increase in the fecal colony forming units (CFU) of Lactobacillus plantarum, Bacillus subtilis, and Saccharomyces cerevisiae compared with those fed cellulose. LPS-treated rats fed PRO showed a significant (p < 0.05) increase in blood secretory immunoglobulin A (sIgA) compared with those not fed PRO. The LPS-treated rats fed PRO resulted in decreased (p < 0.05) blood IL-6 compared with those not fed PRO, indicating that a dietary PRO alleviated inflammatory response in LPS-treated rats. CONCLUSIONS: Dietary oatmeal increased fecal microbes, and PRO supplement resulted in increased intestinal hydrolase and immune functions of the host, demonstrating that soluble PRE with supplemented with PRO could be a more bioactive combination of synbiotics in SD rats.

2.
Lab Anim Res ; 35: 13, 2019.
Article in English | MEDLINE | ID: mdl-32257901

ABSTRACT

A total of 24 SD rats were allotted to four treatment groups such as the control (CON), 1% of cholesterol diet (CHO), 0.5% of coenzyme Q10 (COQ) and 1% of cholesterol plus 0.5% of coenzyme Q10 (CHCQ) groups to determine the effects of coenzyme Q10 (CoQ10) on the antioxidant defense system in rats. The body weight, weight gain, liver weight and abdominal fat pads were unaffected by 0.5% of CoQ10 supplement in the rats. The level of triglyceride and HDL-cholesterol levels in the blood was significantly increased (p < 0.05) by the 1% of cholesterol supplement (CHO), whereas 0.5% of CoQ10 supplement (COQ) did not alter these blood lipid indices. In the mRNA expression, there was a significant effect (P < 0.05) of the CoQ10 supplement on the mRNA expression of superoxide dismutase (SOD), although the mRNA expression of glutathione peroxidase (GPX) and glutathione S-transferase (GST) was unaffected by cholesterol or the CoQ10 supplement. Similar to mRNA expression of SOD, its activity was also significantly increased (P < 0.05) by CoQ10, but not by the cholesterol supplement effect. The activities hepatic GPX and GST were unaffected by CoQ10 and cholesterol supplements in rats. Lipid peroxidation in the CHO group resulted in a significant (p < 0.05) increase compared with that in the other groups, indicating that the CoQ10 supplement to 1% of cholesterol-fed rats alleviated the production of lipid peroxidation in the liver. In conclusion, 0.5% of the CoQ10 supplement resulted in positive effects on the hepatic antioxidant defense system without affecting blood lipid indices in 1% of cholesterol fed rats.

3.
Lab Anim Res ; 34(2): 65-74, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29937913

ABSTRACT

The purpose of the study was to investigate the effects of lipid-coated ZnO (LCZ) and the level of LCZ compared with ordinary zinc oxide (ZnO) on antioxidant defense system in the intestine and liver of piglets. A total of forty piglets (n=8) were fed a diet supplemented with 100 ppm Zn with ZnO (ZnO-1), 2,500 ppm Zn with ZnO (ZnO-2), 100 ppm Zn as LCZ (LCZ-1), 200 ppm Zn as LCZ (LCZ-2), or 400 ppm Zn as LCZ (LCZ-3) for 14-d, respectively. The LCZ-3 group resulted in higher (P<0.05) mRNA expressions and activities of CuZn-superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and glutathione S-transferase (GST) in jejunal mucosa compared with the ZnO-1 and LCZ-1 groups, while no difference was observed in the mRNA level of antioxidant genes between the ZnO-1 and ZnO-2 groups. Within the LCZ groups, the LCZ level linearly and quadratically (P<0.01) increased antioxidant enzymes in the jejunum. The maximum response of jejunal antioxidant enzymes to Zn supplementation was achieved by 400 ppm of LCZ. Hepatic mRNA expression of antioxidant enzymes was unaffected by Zn source and level, while hepatic SOD and GST activities were greater (P<0.05) in the LCZ-3 group than in the ZnO-1 group. No difference was observed in lipid peroxidation of the jejunum and liver and the total antioxidant power of plasma among groups. In conclusion, a supplementation with 400 ppm of LCZ resulted in a maximum increase in antioxidant enzymes, indicating that LCZ may affect antioxidant defense system more profoundly than ZnO.

5.
Asian-Australas J Anim Sci ; 31(3): 403-409, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29268571

ABSTRACT

OBJECTIVE: The present study was conducted to investigate the effects of a lipid-coated zinc oxide (ZnO) supplement Shield Zn (SZ) at the sub-pharmacological concentration on intestinal morphology and gene expression in weanling pigs, with an aim to gain insights into the mechanism of actions for SZ. METHODS: Forty 22-day-old weanling pigs were fed a nursery diet supplemented with 100 or 2,500 mg Zn/kg with uncoated ZnO (negative control [NC] or positive control [PC], respectively), 100, 200, or 400 mg Zn/kg with SZ for 14 days and their intestinal tissues were taken for histological and molecular biological examinations. The villus height (VH) and crypt depth (CD) of the intestinal mucosa were measured microscopically following preparation of the tissue specimen; expression of the genes associated with growth and immune function was determined using the real-time quantitative polymerase chain reaction. RESULTS: There was no difference in daily gain, gain:feed, and diarrhea score between the SZ group and either of NC and PC. The VH and VH:CD ratio were less for the SZ group vs NC in the jejunum and duodenum, respectively (p<0.05). The jejunal mucosal mRNA levels of insulin-like growth factor (IGF-I) and interleukin (IL)-10 regressed and tended to regress (p = 0.053) on the SZ concentration with a positive coefficient, respectively, whereas the IL-6 mRNA level regressed on the SZ concentration with a negative coefficient. The mRNA levels of IGF-I, zonula occludens protein-1, tumor necrosis factor-α, IL-6, and IL-10 did not differ between the SZ group and either of NC and PC; the occludin and transforming growth factor-ß1 mRNA levels were lower for the SZ group than for PC. CONCLUSION: The present results are interpreted to suggest that dietary ZnO provided by SZ may play a role in intestinal mucosal growth and immune function by modulating the expression of IGF-I, IL-6, and IL-10 genes.

6.
Lab Anim Res ; 33(1): 24-31, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28400836

ABSTRACT

The study was performed to see the effects of coenzyme Q10 (CoQ10) on blood biochemical components and hepatic antioxidant system in rats exposed to lipopolysaccharide (LPS)-induced toxicity. A total of 24 rats were allocated to four groups: control (CON), 100 mg/kg BW of LPS (LPS), 100 mg of CoQ10/kg BW with LPS (LCQI) and 300 mg of CoQ10/kg BW with LPS (LCQII). The LPS and LCQI groups showed a significant (P<0.05) increase in the relative spleen weight compared with the CON group without affecting body and liver weights. The blood alanine aminotransferase (ALT) level in the LPS group was significantly (P<0.05) greater than that in the CON group, while supplementation with 100 or 300 mg CoQ10 to rats injected with LPS normalized the ALT level in the CON group. In antioxidant systems, the LPS group showed a significantly (P<0.05) higher mRNA and activity of superoxide dismutase (SOD) than the CON group. The supplementation with CoQ10 to the LPS-treated group normalized the level of SOD, which was comparable to the level of the CON group. Both the mRNA expression and activity of glutathione peroxidase in the LCQI and LCQII groups were higher (P<0.05) than that of the LPS group. However, administration of LPS or CoQ10 unaffected the level of catalase and total antioxidant power. The level of lipid peroxidation in the LCQII group was lower (P<0.05) than that in the LPS group. In conclusion, CoQ10 exerted its favorable effect against liver damage by modulation of antioxidant enzymes in LPS treated rats.

7.
J Anim Sci Technol ; 59: 29, 2017.
Article in English | MEDLINE | ID: mdl-29541479

ABSTRACT

BACKGROUND: Dietary supplementation of zinc oxide (ZnO) to 2000 to 4000 mg/kg is known to be effective for the prevention and treatment of post-weaning diarrhea in the pig. Such a 'pharmacological' supplementation, however, can potentially result in environmental pollution of the heavy metal, because dietary ZnO is mostly excreted unabsorbed. Two experiments (Exp.) were performed in the present study to determine the effects of a lipid-coated ZnO supplement Shield Zn (SZ) compared with those of ZnO. METHODS: In Exp. 1, a total of 240 21-day-old weanling pigs were fed a diet supplemented with 100 mg Zn/kg as ZnO (ZnO-100), ZnO-2500, SZ-100, or SZ-200 in 24 pens for 14 days on a farm with its post-weaning pigs exhibiting a low incidence of diarrhea. Exp. 2 was performed using 192 24-day-old piglets as in Exp. 1 on a different farm, which exhibited a high incidence of diarrhea. RESULTS: In Exp. 1, fecal consistency (diarrhea) score (FCS) was less for the ZnO-2500 and SZ-200 groups than for the SZ-100 group (P < 0.05), with no difference between the SZ-100 and ZnO-100 groups. Both average daily gain (ADG) and gain:feed ratio were less for the SZ-200 group than for the ZnO-2500 group, with no difference between the ZnO-100 group and SZ-100 or SZ-200 group. The villus height (VH), crypt depth (CD), and VH:CD ratio of the intestinal mucosa were not influenced by the treatment. In Exp. 2, FCS was lowest for the ZnO-2500 group, with no difference among the other groups. However, neither the ADG nor gain:feed ratio was influenced by the treatment. CONCLUSION: Results suggest that physiological SZ supplementation has less beneficial effects than pharmacological ZnO for the alleviation of diarrhea irrespective of its severity and for promoting growth without influencing their integrity of the intestinal mucosal structures with little advantage over physiological ZnO in weanling pigs with a small pen size.

8.
Lab Anim Res ; 31(3): 117-24, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26472964

ABSTRACT

This study was conducted to investigate the effects of lutein alone or in combination with vitamin C on the antioxidant defense system in rats. A total of 18 eight-week-old male Sprague Dawley (SD) rats were randomly assigned to three groups for 4 weeks: control (CON), lutein (LUT, 50 mg lutein/kg BW) and lutein plus vitamin C (LVC, 50 mg lutein/kg BW+1,000 mg vitamin C/kg BW). No differences in body weight, relative live weight or plasma biochemical profiles were observed among treatment groups. In the hepatic antioxidant defense systems, the mRNA expression of superoxide dismutase (SOD) in the LUT and LVC groups was significantly (P<0.05) higher than that in the CON group, whereas the mRNA level of glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) was not affected by the administration of antioxidants. SOD and GST activities in the LUT and LVC groups were significantly higher (P<0.05) than those in the CON group, whereas GPX, CAT and lipid peroxidation did not differ among groups. In addition, the LVC group showed a significant (P<0.05) increase in plasma and hepatic total antioxidant power (TAP) relative to the CON group. Overall, administration of lutein in combination with vitamin C improved the status of the total antioxidant defense system in SD rats.

9.
Asian-Australas J Anim Sci ; 27(5): 749-56, 2014 May.
Article in English | MEDLINE | ID: mdl-25050011

ABSTRACT

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between 32°C to 34°C at day to 27°C to 29°C at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

10.
Anim Sci J ; 85(8): 805-13, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24799095

ABSTRACT

This study was aimed to evaluate the effect of dietary supplementation of lipid-encapsulated (coated) zinc oxide ZnO on post-weaning diarrhea (colibacillosis) in weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two 35-day-old weaned piglets were orally challenged with 3 × 10(10) colony forming units of ETEC K88 while eight piglets received no challenge (control). Each eight challenged piglets received a diet containing 100 ppm ZnO (low ZnO), 2500 ppm ZnO (high ZnO) or 100 ppm of lipid (10%)-coated ZnO (coated ZnO) for 7 days; control pigs received the low ZnO diet. Daily gain, goblet cell density in the villi of the duodenum, jejunum and ileum, and villus height in the jejunum and ileum, which decreased due to the challenge, were equally greater in the coated ZnO and high ZnO groups versus low ZnO group. Fecal consistency score, serum interleukin-8 concentration, subjective score of fecal E. coli shedding, and digesta pH in the stomach, jejunum and ileum, which increased due to the challenge, were equally low in the coated ZnO and high ZnO groups versus low ZnO. Results suggest that a low level of coated ZnO might well substitute for a pharmacological level of native ZnO in dietary supplementation to alleviate colibacillosis of weaned piglets.


Subject(s)
Diarrhea/therapy , Diarrhea/veterinary , Dietary Supplements , Escherichia coli Infections , Escherichia coli , Gastroenteritis/microbiology , Gastroenteritis/veterinary , Intestines/growth & development , Swine Diseases/therapy , Swine , Zinc Oxide/administration & dosage , Animals , Gastroenteritis/therapy , Hydrogen-Ion Concentration , Intestines/cytology , Intestines/microbiology , Weaning
11.
J Anim Sci Technol ; 56: 29, 2014.
Article in English | MEDLINE | ID: mdl-26290718

ABSTRACT

This study compared the effects of varying lipid content and dietary concentration of a lipid-encapsulated (LE) ZnO product to those of native ZnO and thereby to find insights into optimal lipid coating and dosage of the Zn supplement. A total of 192 21-d-old weanling pigs were allotted to 48 pens, after which each six pens received a ZnO-free basal diet supplemented with 125 ppm ZnO (100 ppm Zn; BASAL), 2,500 ppm Zn as native ZnO (HIGH), or 100 or 200 ppm Zn as LE ZnO (LE-100 or LE-250) containing 8%, 10%, or 12% lipid [LE-8%, LE-10%, or LE-12%, respectively; 2 × 3 factorial arrangement within the LE-ZnO diets (LE-ALL)] for 14 d. Forty pigs were killed at the end for histological and biochemical examinations. None of ADG, ADFI, gain:feed, and fecal consistency score differed between the LE-ALL and either of the BASAL and HIGH groups. Hepatic and serum Zn concentrations were greater (p <0.05) in the HIGH vs. LE-ALL group, but did not differ between LE-ALL and BASAL, between LE-100 and -250, or among LE-8%, -10%, and -12% groups. Villus height (VH), crypt depth (CD), and the VH:CD ratio in the duodenum, jejunum, and ileum did not differ between the LE-ALL and either of the BASAL and HIGH groups, except for a greater CD in the duodenum in the LE-ALL vs. HIGH group. Additionally, VH and CD in the duodenum and VH:CD in the jejunum were greater in the LE-250 vs. LE-100 group. Specific activities of sucrase, maltase, and leucine aminopeptidase in these intestinal regions and those of amylase and trypsin in the pancreas were not influenced by the lipid content or dietary concentration of LE ZnO and also did not differ between the LE-ALL and either of the BASAL and HIGH groups, except for a greater pancreatic amylase activity in the former vs. HIGH group. In conclusion, the present results indicate that the LE ZnO, regardless of its lipid percentage or supplementation level examined in this study, has no significant effect on growth performance, fecal consistency, or digestive enzyme activities of weanling pigs under the experimental conditions.

12.
Curr Drug Targets ; 14(9): 999-1005, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23574281

ABSTRACT

Carotenoids are considered to act as antioxidants and protect humans from serious disorders such as skin degeneration and ageing, cardiovascular disease, certain types of cancer, and age-related diseases of the eye. In this study, these chemopreventive activities of a carotenoids-overexpressing transgenic carrot were evaluated. The results of DPPH, hydroxyl, and superoxide radical scavenging tests demonstrate that the acetone extract obtained from the taproots of the carrot plants exhibits significant antioxidant activity. A higher activity was detected in the transgenic carrot extract compared with the wild-type extract. A chemopreventive activity test for degenerative diseases of the eye revealed that pretreatment with the carrot extract reduced cell death in a retinal ganglion cell line, RGC-5 cells exposed to 1-buthionine- (R,S)-sulfoximine and L-glutamic acid.


Subject(s)
Antioxidants/pharmacology , Carotenoids/pharmacology , Daucus carota/genetics , Plant Extracts/pharmacology , Protective Agents/pharmacology , Retinal Ganglion Cells/drug effects , Acetone , Antioxidants/chemistry , Antioxidants/metabolism , Biphenyl Compounds , Buthionine Sulfoximine/pharmacology , Carotenoids/analysis , Cell Death , Cell Line , Daucus carota/metabolism , Glutamic Acid/pharmacology , Humans , Hydroxyl Radical/metabolism , Oxidative Stress , Picrates , Plant Extracts/chemistry , Plant Roots/genetics , Plant Roots/metabolism , Plants, Genetically Modified , Retinal Ganglion Cells/physiology , Superoxides/metabolism
13.
Exp Anim ; 61(5): 543-53, 2012.
Article in English | MEDLINE | ID: mdl-23095818

ABSTRACT

A total of 21 male SD rats were divided into three groups to investigate the effects of consecutive cyclic heat stress or vitamin C under heat stress on heat shock protein (HSP) 70, inflammatory cytokines, and antioxidant systems. The heat stress (HS) and vitamin C supplementation during heat stress (HS+VC) groups were exposed to cyclic heat stress (23 to 38 to 23°C) for 2 h on each of seven consecutive days. The HS+VC group had free access to water containing 0.5% vitamin C throughout the experiment. Hepatic HSP70 mRNA in the HS group was significantly (P<0.05) higher than that in the control (CON) or HS+VC group. The mRNA levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the HS group were greater (P<0.05) than those in the CON group. The HS+VC group showed significantly (P<0.05) lower mRNA levels of hepatic interleukin-6 and TNF-α than the HS group. However, thymic HSP70 and inflammatory cytokines were unaffected by treatments. In the hepatic antioxidant system, the mRNA and activity of glutathione peroxidase (GPX) were greater (P<0.05) in the HS than in the CON group, whereas the HS+VC group showed markedly (P<0.05) lower GPX mRNA and activity than the HS group. However, superoxide dismutase, glutathione S-transferase, and malondialdehyde were unaffected by treatments. In conclusion, cyclic heat stress activated hepatic HSP70, TNF-α, iNOS, and GPX genes, whereas vitamin C during heat stress ameliorated heat stress-induced cellular responses in rats.


Subject(s)
Antioxidants/metabolism , Ascorbic Acid/administration & dosage , Cytokines/metabolism , HSP70 Heat-Shock Proteins/metabolism , Heat-Shock Response , Rats/physiology , Animals , Dietary Supplements/analysis , Hot Temperature/adverse effects , Immunoenzyme Techniques , Male , Organ Specificity , RNA, Messenger/metabolism , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
14.
Int J Mol Med ; 20(6): 829-35, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17982690

ABSTRACT

To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by a real-time reverse transcription-polymerase chain reaction. Two hundred and fifty-one and 73 genes were up- and down-regulated, respectively by insulin in H1/siRNAinsulin-CMV/hIDE Tg mice compared to the controls. Genes encoding for physiological processes, extracellular defense response and response to biotic stimuli were significantly over-represented in the up-regulated group. Among the down-regulated transcripts, those encoding for extracellular matrix proteins were dramatically over-represented, followed by those related to monooxygenase and oxidoreductase activities. The major genes in the up-regulated categories included Egr1, Saa2, Atf3, DNAJB1 and cCL2, whereas those in the down-regulated categories were Cyp17a1, Adn, Gadd45g, Eno3 and Moxd1. These results indicate that the microarray analysis identifies several gene functional groups and individual genes that respond to a sustained reduction in the insulin levels in the livers of Tg mice. These results also suggest that microarray testing is a useful tool for the better understanding of insulin-regulated diabetes-related diseases.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation , Insulin/metabolism , Insulysin/metabolism , Liver/physiology , Mice, Transgenic , RNA, Small Interfering/metabolism , Animals , Humans , Insulin/genetics , Insulysin/genetics , Mice , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , RNA, Small Interfering/genetics
15.
J Biosci ; 32(4): 723-35, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17762145

ABSTRACT

To investigate whether selenium (Sel) treatment would impact on the onset of diabetes,we examined serum biochemical components including glucose and insulin,endoplasmic reticulum (ER) stress and insulin signalling proteins, hepatic C/EBP-homologous protein (CHOP) expression and DNA fragmentation in diabetic and non- diabetic conditions of non-obese diabetic (NOD) mice. We conclude that (i) Sel treatment induced insulin-like effects in lowering serum glucose level in Sel-treated NOD mice, (ii) Sel-treated mice had significantly decreased serum biochemical components associated with liver damage and lipid metabolism, (iii) Sel treatment led to the activation of the ER stress signal through the phosphorylation of JNK and eIF2 protein and insulin signal mechanisms through the phosphorylation of Akt and PI3 kinase, and (iv) Sel-treated mice were significantly relieved apoptosis of liver tissues indicated by DNA fragmentation assay in the diabetic NOD group. These results suggest that Sel compounds not only serve as insulin-like molecules for the downregulation of glucose level and the incidence of liver damage, but may also have the potential for the development of new drugs for the relief of diabetes by activating the ER stress and insulin signalling pathways.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/metabolism , Down-Regulation/drug effects , Endoplasmic Reticulum/metabolism , Insulin/metabolism , Selenium/pharmacology , Signal Transduction , Animals , Blood Glucose/analysis , Body Weight/drug effects , Insulin/blood , Mice , Mice, Inbred NOD
16.
Int J Mol Med ; 19(1): 65-73, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17143549

ABSTRACT

The dual expression system for the suppression and clearance of insulin has not been previously used to produce transgenic mice for diabetes-related disease. The aim of this study was to produce new transgenic mice coexpressing specific insulin small interfering RNA (siRNA) sequences and the human insulin degrading enzyme (hIDE) gene in order to examine the diabetes-like phenotype. To achieve this, a new lineage of transgenic mice was produced by the microinjection of the dual expression constructs (pH1/siRNAinsulin-CMV/hIDE) into mouse fertilized eggs. The results showed that overexpressing the insulin siRNA and hIDE genes resulted in the induction of the human enzyme, impaired glucose tolerance and lower serum insulin levels compared to the Non-Tg mice. Moreover, the Tg mice aged 20 weeks had a significantly activated ER stress signaling compared to their Non-Tg counterparts, which may be associated with the suppression of insulin production in the pancreas and the degradation of insulin in the liver, respectively. Therefore, insulin-suppressed transgenic mice can be used to examine diabetes as a new diabetes-like phenotype model, which results in a lower level of circulating insulin without the destruction of pancreatic islets.


Subject(s)
Endoplasmic Reticulum/metabolism , Glucose Intolerance/metabolism , Insulin/blood , Insulysin/metabolism , RNA, Small Interfering/metabolism , Signal Transduction , Animals , Base Sequence , Female , Genetic Vectors/genetics , Glucose Intolerance/genetics , Glucose Tolerance Test , Insulin/genetics , Insulysin/genetics , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Molecular Sequence Data , Pancreas/metabolism , Postprandial Period , Tissue Distribution
17.
Exp Anim ; 52(2): 99-107, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12806884

ABSTRACT

The primary aim of the present study was to define central and peripheral physiological differences between dietary obesity-susceptible (DOS) and obesity-resistant (DOR) outbred Sprague Dawley (SD) rats when given a moderate high fat diet containing 32.34% of energy as a fat. After a 9-week feeding period, the DOS-SD rats consumed significantly more feed (11.1%) and had higher abdominal (39.9%) and epididymal (27.5%) fat pads than the DOR-SD rats. In addition, serum leptin and insulin levels were significantly increased in the DOS-SD rats compared with those in the DOR-SD rats. However, we did not observe significant differences in serum triglyceride, cholesterol and glucose. No differences in hypothalamic OB-Ra and Rb mRNA expressions were found between the two groups. In contrast, arcuate NPY immunohistochemical expression was much higher in the DOS-SD rats than in the DOR-SD rats, though NPY expression in the supraoptic and paraventricular nuclei was not different between the two phenotypes. In peripheral tissues, the DOS-SD rats showed noticeably increased acetyl CoA carboxylase (ACC) mRNA expression in the liver, not epididymal fat. However, Western blot of peroxisomal proliferator activated factor gamma (PPAR gamma) in the liver and epididymal fat was not different between the two phenotypes of SD rats. It was concluded that different body weight phenotypes within outbred SD population responded differently to the development of dietary induced obesity via altered anabolic features in the hypothalamus and liver.


Subject(s)
Diet , Genetic Predisposition to Disease , Obesity/etiology , Acetyl-CoA Hydrolase/genetics , Animals , Base Sequence , Cholesterol/blood , DNA Primers , Immunohistochemistry , Insulin/blood , Leptin/blood , Male , Obesity/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Receptors, Cell Surface/genetics , Receptors, Leptin , Triglycerides/blood
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