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1.
M I Hawa M G Valorani L R Buckley P E Beales A Afeltra F Cacciapaglia R D Leslie P Pozzilli 《Hormones et métabolisme》2004,36(9):620-624
BACKGROUND AND AIMS: Several studies have suggested that vitamin D supplementation in early life may reduce the risk of developing type 1 diabetes in later life. The non-obese diabetic (NOD) mouse is a model of spontaneous type 1 diabetes currently used for testing hypothesis/compounds aimed at disease prevention. In this study, we tested the effect of vitamin D (16 IU by gavage) on diabetes incidence in NOD/Ba mice treated from conception with olive oil containing vitamin D via maternal dosing up to 10 weeks of age and followed up until 32 weeks of age. METHODS: Twelve breeding pairs were administered olive oil containing vitamin D during pregnancy, 15 days following the birth of the pups and for the next 10 weeks subsequently. The same breeding pairs were bred again after a clearance period of 15 days using a control solution to produce a control litter. This control group received a control solution for the same period of time. Diabetes incidence, degree of insulitis, and insulin content in the pancreas were investigated in the two groups. RESULTS: 12 vitamin D-treated NOD mice developed diabetes compared to 15 animals in the control group (Log rank test p = 0.899, NS). There were no significant differences between the groups in diabetes incidence, time of onset of the disease, degree of insulitis, or the insulin content in the pancreas. CONCLUSION: Vitamin D administered in utero and in the early stages of life at the dosage used does not change the incidence of diabetes or modify the disease process that leads to beta cell destruction in the NOD mouse. 相似文献
2.
Spontaneous diabetes in the NOD mouse can be
prevented by nicotinamide or by an infant formula
diet in which the protein source is replaced with
casein hydrolysate (Pregestimil) or soy protein
(Prosobee). NOD mice maintained on the standard
diet (chow and water) and given cyclophosphamide
(Cy) at day 95 develop accelerated and synchronised
diabetes within 14 days. Here, we compared the
ability of oral nicotinamide or Prosobee, either given
alone or concurrently, from weaning, in preventing
diabetes in the Cy model. The resulting insulitis and
the expression of intra-islet inducible nitric oxide
synthase (iNOS) were examined at days 0, 4, 7, 11
and 14 following Cy administration. Intra-islet CD4
and CD8 cells and macrophages were also enumerated
at day 11. In mice given the standard diet and
injected with Cy at day 95 (group 5), diabetes
developed in 7/11 mice, 14 days later. Mice exposed
to oral nicotinamide (group 2), Prosobee (group 3) or
both (group 4), did not develop the disease during
this period and until a further 30 days (p = 0.03). In
mice exposed to the standard diet and without Cy
treatment (group 1) the insulitis scores increased
slowly until day 11 and then declined slightly at day
14 whereas mice exposed to the same diet but given
Cy at day 95, showed a sharp decline at day 4
followed by a rapid increase between day 7–14.
However, in mice given either nicotinamide, Prosobee
or both, the insulitis scores at most time-points
were generally lower than in Cy-teated animals on
the standard diet. In the latter group, CD4 and CD8
cells and macrophages were also higher at day 11
than all other 4 groups (CD4: p < 0.05; CD8: p < 0.05;
macrophages: p < 0.0001). The number of iNOS
labelled cells increased progressively in mice on
the standard diet and given Cy and were significantly
higher at days 4, 7 and 11 than in the 3 dietary
groups. Thus, oral nicotinamide or Prosobee, either
alone or together, prevents Cy induced diabetes in
the NOD mouse. The protective diets suppress Cyinduced
intra-islet immune cell influx and iNOS
expression. 相似文献
3.
4.
Mohamed Saber Tarek Diab Olft Hammam Amr Karim Amina Medhat Mamdouh Khela Ehab El-Dabaa 《The Korean journal of parasitology》2013,51(2):155-163
This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic
expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously
(SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected
in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted
in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection. 相似文献
5.
Juan P. Damián Victoria Acosta Maira Da Cu?a Isara Ramírez Natalia Oddone Ana Zambrana Verónica Bervejillo Juan C. Benech 《Experimental Animals》2014,63(3):277-287
The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV)
on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and
fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after
STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4
weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM).
In the second week of RSV treatment, a higher grooming frequency
(P<0.05) and a lower defecation and rearing frequency
(P<0.05) were detected in the OFT in the RDM group compared with the
DM. There was a higher grooming frequency (P<0.05) and higher
percentage of entries in open arms (P<0.05) in the RDM group than in
the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect
observed was a higher grooming frequency in the RDM group than in the DM group
(P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice
provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were
observed in a short time window (2 weeks). It is suggested that RSV may help diabetic
animals to adapt to new stressing and anxiety situations and thus to improve their
welfare. 相似文献
6.
Daniel Landau Yael Segev Rina Eshet Allan Flyvbjerg Moshe Phillip 《Experimental diabetes research》2000,1(1):9-18
We investigated the changes in GH-IGF-I axis in
non-obese diabetic (NOD)-mice, a model of insulin dependent
diabetes mellitus. Diabetic female NOD
mice and their age- and sex-matched controls were
sacrificed at 4, 14, 21 and 30 days (30d DM) after the
onset of glycosuria. Serum GH levels increased and
serum IGF-I levels decreased in the 30d DM group
(182 ± 32% and 45 ± 24% of age-matched controls
respectively, p < 0.05). Another group (30d DM + I)
was given SC insulin, and its serum IGF-I levels
remained decreased. Liver GH receptor (GHR) and
GH binding protein (GHBP) mRNA levels, as well
as liver membrane GH binding assays were deeply
decreased in the 30d DM group in comparison to
controls. GHR message and binding capacity remained
decreased in the 30d DM + I group. Renal
GHR mRNA was decreased at 21d DM but not at
14d DM, whereas GHBP mRNA remained unchanged
throughout the experiment. In conclusion,
increased serum GH levels are documented in NOD
diabetic mice, similarly to the changes described in
humans. The decrease in GHR levels and decreased
serum IGF-I in spite of increased circulating GH
suggest a state of GH resistance. 相似文献
7.
Manuel T. Velasquez Sam J. Bhathena Carl T. Hansen 《Experimental diabetes research》2001,2(3):217-223
The spontaneously hypertensive/NIH-corpulent
(SHR/N-cp) rat is a genetic animal model that exhibits
obesity, metabolic features of hyperinsulinemia,
hyperglycemia, and hyperlipidemia, which are
characteristic of type II diabetes and mild hypertension.
To determine the role of leptin, the protein
product of the ob gene, in the development of obesity
and diabetes in this model, we measured
steady-state circulating levels of leptin in obese and
lean SHR/N-cp rats and examined the relation
between plasma leptin levels and metabolic variables
at the stage of established obesity in these animals.
Mean fasting plasma leptin concentration was
8-fold higher in obese than in lean rats (p<0.01).
This was associated with a 6-fold elevation in
plasma insulin in the obese group. Fasting levels of
plasma glucose, cholesterol, and triglyceride were
all significantly higher in obese rats than in lean
controls. Spearman correlation analysis showed a
significant positive correlation between plasma leptin
concentration and body weight among the animals
(r=0.73, p<0.01). Similarly, plasma insulin
concentration was significantly correlated with BW
in all animals (r=0.54, p<0.05). There was also a
significant positive.correlation between plasma leptin
and plasma insulin in the entire group (r=0.70,
p<0.01). However, this relationship was significant
only for lean rats but not for obese rats (r=0.59,
p<0.05 for lean rats, and r=0.23, p=NS, for obese
rats). Plasma leptin also correlated positively with
fasting plasma glucose (r=0.75, p<0.05), total cholesterol
(r=0.63, p<0.05), and triglyceride (r=0.67,
p <0.05). The marked elevation of plasma leptin in
obese SHR/N-cp rats suggests that obesity in this
animal model is related to up-regulation of the ob
gene. Circulating leptin appears to be one of the
best biological markers of obesity and that hyperleptinemia
is closely associated with several metabolic
risk factors related to insulin resistance in the
diabesity syndrome. 相似文献
8.
Britt Tranberg Lars I. Hellgren Jens Lykkesfeldt Kristen Sejrsen Aymeric Jeamet Ida Rune Merete Ellekilde Dennis S. Nielsen Axel Kornerup Hansen 《PloS one》2013,8(8)
An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001–0.05). Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001). Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01) and glucose clearance was improved after an oral glucose challenge (P<0.05). Plasma cholesterol was lowered by whey compared to casein (P<0.001). The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05) whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey. 相似文献
9.
Kleiton Augusto dos Santos Silva Rafael da Silva Luiz Rodolfo Rosseto Rampaso Nayda Parísio de Abreu édson Dias Moreira Cristiano Teixeira Mostarda Kátia De Angelis Vicente de Paulo Castro Teixeira Maria Cláudia Irigoyen Nestor Schor 《PloS one》2012,7(11)
Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p<0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p<0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p<0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p<0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ. 相似文献
10.
Background
We and others have previously demonstrated that treatment with bone marrow derived DC genetically modified to express IL-4 reduce disease pathology in mouse models of collagen-induced arthritis and delayed-type hypersensitivity. Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC, genetically modified to express interleukin 4 (IL-4), reduces the onset of hyperglycemia in a significant number of animals. However, the mechanism(s) through which DC expressing IL-4 function to prevent autoimmune diabetes and whether this treatment can reverse disease in pre-diabetic NOD mice are unknown.Methodology/Principal Findings
DC were generated from the bone marrow of NOD mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL-4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice were segregated into normoglycemic (<150mg/dL) and prediabetic groups (between 150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for adoptive transfer of 106 DC via a single i.v. injection. A single injection of DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but not control DC, decreased the number of mice progressing to diabetes when given to prediabetic NOD mice 12–16 weeks of age. DC/sIL-4 treatment also significantly reduced islet mononuclear infiltration and increased the expression of FoxP3 in the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4 treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by ELISPOT of splenocytes in treated animals.Conclusions
Adoptive transfer of DC transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an effective treatment for T1D. 相似文献11.
The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was then performed and after 14 days, tracheal responsiveness, concentration of interleukin-8 (IL-8) in serum and broncho-alveolar lavage fluid (BALF), as well as total and differential white blood cells (WBC) counts were evaluated. Tracheal responsiveness, total WBC counts, neutrophil and eosinophil percentage in BALF as well as concentration of IL-8 in serum and BALF significantly increased but lymphocyte percentage decreased in COPD compared to the control group (P<0.05 to p<0.001). Cell therapy was able to restore the tracheal hyper-responsiveness and the increased IL-8 concentration in serum and BALF of COPD-ITASC but not COPD-IVASC animals (P<0.05 for all cases). Total WBC in BALF also showed a significant decrease in both treated groups and the percentages of eosinophils, neutrophils and lymphocytes in BALF were reversed in COPD-ITASC compared to COPD-ITPBS animals (P<0.05 to P<0.001). Therefore, intratracheal cell therapy with ASC can decrease tracheal hyperresponsiveness and lung inflammation in cigarette smoke induced-COPD which may be helpful in attenuation of the severity of disease in patients suffering from COPD. 相似文献
12.
Qianqian Sun Shuangshuang Nie Lingxiao Wang Fan Yang Zhangming Meng Hengyi Xiao Bing Xiang Xiujun Li Xianghui Fu Shuang Wang 《PloS one》2016,11(3)
Aging may be a risk factor for type 2 diabetes in the elderly. Dietary intervention can affect glucose tolerance in adults, which may be due to body composition and islet cell autophagy. The aim of this study was to determine the effects of various dietary interventions on islet cell autophagy. Pancreatic tissue and blood samples were collected from Sprague Dawley rats (14–16 months old, n = 15 for each group) that received a normal diet (ND), a high-fat diet (HFD), or a calorie-restricted diet (CRD). The body weight (BW), visceral fat, serum lipid levels, fasting serum glucose, insulin levels, and β/α cell area were determined in 14-16-(0-w), 16-18-(8-w), and 18-20(16-w)-month-old rats. Pancreatic islet autophagy (LC3B and LAMP2), AP (Acid Phosphatase) and apoptosis (apoptosis index, AI (TUNEL assay) and cleaved caspase-3) were detected using immunohistochemistry, ELISA and western blot. At 16 weeks, the expressions of LC3B, LAMP2 and AP markedly increased in both the HFD (P<0.01) and CRD (P<0.05) groups; however, an increase in the AI (P<0.05), cleaved caspase-3 and Beclin1 expression and a decrease in the expressions of BCL2 and BCLXL (P<0.05) were observed in only the HFD group. FFA, triglyceride levels, HOMA-IR, insulin levels and glucagon levels were significantly increased in the HFD group but decreased in the CRD group at 16 weeks (P<0.05). The degree of islet cell autophagy was potentially regulated by the levels of FFA and islet cell insulin and glucagon, which may have been due to the effects of Beclin1/BCL2. 相似文献
13.
Patricia de Godoy Bueno Juliana Navarro Ueda Yochite Graziela Fernanda Derigge-Pisani Kelen Cristina Ribeiro Malmegrim de Farias Lucimar Retto da Silva de Avó Júlio César Voltarelli ?ngela Merice de Oliveira Leal 《PloS one》2015,10(4)
The purpose of this study was to investigate the effects of multiple infusions of allogeneic MSCs on glucose homeostasis and morphometry of pancreatic islets in high- fat diet (HFD) fed mice. Swiss mice were fed standard diet (C group) or HFD (HFD group). After 8 weeks, animals of HFD group received sterile phosphate-buffered saline infusions (HFD-PBS) or four infusions of MSCs one week apart (HFD-MSCs). Fasting glycemia (FG) was determined weekly and glucose (GTT) and insulin (ITT) tolerance tests were performed 4, 8, 12, and 16 weeks after the infusions of MSCs. The MSCs transplanted mice were classified as responder (FG < 180 mg/dL, 72.2% of transplanted mice) or non-responder (FG > 180mg/dL, 28.8%) Seven weeks after MSCs infusions, FG decreased in HFD-MSCs responder mice compared with the HFD-PBS group. Sixteen weeks post MSCs infusions, GTT and ITT areas under the curve (AUC) decreased in HFD-MSCs responder mice compared to HFD-PBS group. Serum insulin concentration was higher in HFD-PBS group than in control animals and was not different compared with the other groups. The relative volume of α-cells was significantly smaller in HFD-PBS group than in C group and significantly higher in HFD-MSCs-NR than in HFD-PBS and HFD-MSCs-R groups. Cell apoptosis in the islets was higher in HFD-PBS group than in C group, and lower in HFD-MSCs responder mice than in HFD-PBS group and non-responder animals. The results demonstrate the ability of multiple infusions of MSCs to promote prolonged decrease in hyperglycemia and apoptosis in pancreatic islets and increase in insulin sensitivity in HFD fed mice. 相似文献
14.
As the study of type 1 diabetes moves towards preventive therapy, the role of adjuvants needs to be addressed. Incomplete Freund's adjuvant (IFA) is thought of as "immunologically inert" as, unlike complete FA (CFA), it has no components designed to provoke an immune response. We investigated the effect of IFA as an immunomodulator on the disease process leading to type 1 diabetes in the non-obese diabetic (NOD) mouse. 24 NOD mice were injected intradermally (i.d.) at 8 and 12 weeks of age with a 1:1 mixture of IFA and saline; 24 controls received saline alone. Splenocytes were tested against antigens thought to be involved in the disease process, namely insulin, a GAD peptide, a beta-casein peptide, a Glut-2 peptide and concanavalin A (ConA) as a non-specific antigen. In the IFA experiment diabetes incidence was 13% compared to 38% in the controls (p < 0.05). In vitro, splenocytes from IFA treated animals showed non-specific immunosuppression with ConA (p < 0.01), whereas the response to 1-casein and Glut-2 was raised in IFA treated animals with respect to controls. ELISA using supernatants from IFA treated animals, showed a typical Th2 cytokine pattern, whereas controls showed a Th1 pattern. In conclusion, IFA alone can reduce diabetes incidence in the NOD mouse apparently by modulating the immune response towards beta-cell related specific antigens. As IFA has been adopted as an adjuvant in preventive trials in the NOD mouse, this might have implications for the interpretation of previous and future results. 相似文献
15.
Xiu-feng Hua Yan-wei Wang Yu-xiao Tang Sheng-qiang Yu Shao-hua Jin Xiao-mei Meng Hua-feng Li Fu-jun Liu Qiang Sun Hai-yan Wang Jian-yuan Li 《PloS one》2014,9(7)
Background
Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs), a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs) differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID)/non-obese diabetic (NOD) mice, an animal model of diabetes.Methods
We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5–7×106 differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n = 20). The control group were transplanted with undifferentiated hESCs (n = 6). Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels.Results
The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature β cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ≥8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001).Conclusions
The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct hyperglycemia in SCID/NOD mice for ≥8 weeks. 相似文献16.
Stephanie Busch Aimo Kannt Matthias Kolibabka Andreas Schlotterer Qian Wang Jihong Lin Yuxi Feng Sigrid Hoffmann Norbert Gretz Hans-Peter Hammes 《PloS one》2014,9(7)
Rats expressing a transgenic polycystic kidney disease (PKD) gene develop photoreceptor degeneration and subsequent vasoregression, as well as activation of retinal microglia and macroglia. To target the whole neuroglialvascular unit, neuro- and vasoprotective Erythropoietin (EPO) was intraperitoneally injected into four –week old male heterozygous PKD rats three times a week at a dose of 256 IU/kg body weight. For comparison EPO-like peptide, lacking unwanted side effects of EPO treatment, was given five times a week at a dose of 10 µg/kg body weight. Matched EPO treated Sprague Dawley and water-injected PKD rats were held as controls. After four weeks of treatment the animals were sacrificed and analysis of the neurovascular morphology, glial cell activity and pAkt localization was performed. The number of endothelial cells and pericytes did not change after treatment with EPO or EPO-like peptide. There was a nonsignificant reduction of migrating pericytes by 23% and 49%, respectively. Formation of acellular capillaries was significantly reduced by 49% (p<0.001) or 40% (p<0.05). EPO-treatment protected against thinning of the central retina by 10% (p<0.05), a composite of an increase of the outer nuclear layer by 12% (p<0.01) and in the outer segments of photoreceptors by 26% (p<0.001). Quantification of cell nuclei revealed no difference. Microglial activity, shown by gene expression of CD74, decreased by 67% (p<0.01) after EPO and 36% (n.s.) after EPO-like peptide treatment. In conclusion, EPO safeguards the neuroglialvascular unit in a model of retinal neurodegeneration and secondary vasoregression. This finding strengthens EPO in its protective capability for the whole neuroglialvascular unit. 相似文献
17.
[Purpose]
This study investigated the effects of high-intensity exercise (Ex) and high dietary fat intake on lipid metabolism in the liver of rats.[Methods]
Male Sprague-Dawley rats were randomly assigned to one of the four groups (n=10 per group) that were maintained on a normal diet (ND) or high-fat diet (HFD) consisting of 30% fat (w/w), with or without exercise on a treadmill at 30 m/min and 8% grade) for 4 weeks (i.e., ND, ND+Ex, HFD, and HFD+Ex groups).[Results]
Body weight (p<.001), total plasma cholesterol (TC) (p<.001), triglyceride (TG) (p<.05), and liver TG levels (p<.05) were increased in the HFD group relative to the ND groups, and serum glucose (p<.05), insulin (p<.05), homeostatic model assessment of insulin resistance (HOMA-IR) (p<.01), and liver TG levels (p<.01) were also higher in the HFD group compared to the ND+Ex group. Plasma free fatty acid was elevated in the HFD+Ex group compared to the HFD group (p<.01). With the exception of acetyl coenzyme A carboxylase, the expression of lipid metabolism-related genes in the liver was altered in the Ex groups compared to the control group (p<.05), with genes involved in lipolysis specifically up regulated in the HFD+Ex group compared to the other groups.[Conclusion]
Vigorous exercise may increase glucose utilization and fat oxidation by activating genes in the liver that are associated with lipid metabolism compared to that in animals consuming a HFD without exercise. Therefore, high intensity exercise can be considered to counter the adverse effects of high dietary fat intake. 相似文献18.
J Krug E F Lampeter A J Williams E Procaccini C Cartledge A Signore P E Beales P Pozzilli 《Hormones et métabolisme》1992,24(1):1-4
Ciamexon (CMX), a new immunomodulatory compound acting mainly on B-lymphocytes was given orally to 42 NOD mice divided into three sex and litter matched groups (A: 0.3 mg/mouse/day CMX, B: 1.5 mg/mouse/day CMX, C: control) from 7 weeks of age. Animals were followed up for evaluation of diabetes incidence up to 32 weeks of age. There was a tendency for a delayed onset of hyperglycemia in mice of group B up to 26 weeks of age; however no significant difference in the cumulative incidence of diabetes at 32 weeks of age was observed (A: 57.5%, B: 38.5%, C: 38.5%). No differences were found in the number of infiltrated islets in animals culled at 10 weeks of age treated with CMX from 4 weeks of age. We conclude that CMX does not modify the course of insulitis and diabetes incidence in NOD mice although though the appearance of glycosuria was delayed by this treatment. 相似文献
19.
Mércia Beluzi Sidney B. Peres Felipe S. Henriques Rogério A. L. Sertié Felipe O. Franco Kaltinaitis B. Santos Pamela Knobl Sandra Andreotti Cláudio S. Shida Rodrigo X. Neves Stephen R. Farmer Marília Seelaender Fábio B. Lima Miguel L. Batista Jr. 《PloS one》2015,10(3)
Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia. 相似文献