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1.
In Koo Hwang Il Yong Kim Eun Jung Joo Jae Hoon Shin Ji Won Choi Moo-Ho Won Yeo Sung Yoon Je Kyung Seong 《Neurochemical research》2010,35(4):645-650
In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes,
on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker
diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to
14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels
were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly
decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin
(DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in
the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG
compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation
and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and
neuroblast differentiation in the SZDG in diabetic rats. 相似文献
2.
It has recently been reported that diabetes mellitus is strongly associated with neurodegenerative and functional disorders
of the central nervous system. In the present study, we investigated the changes in proliferating neurons in the dentate gyrus
of type II diabetic rats using doublecortin (DCX), a marker of progenitors differentiating into neurons. At 4 weeks after
birth, there were no differences in the blood glucose levels of Zucker diabetic fatty (ZDF) rats or Zucker lean control (ZLC)
rats. DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in both the ZDF and ZLC rats;
however, DCX immunoreactivity was higher in the ZLC rats than in the ZDF rats. At 12 weeks after birth, the blood glucose
level was significantly increased by 400 mg/dl in the ZDF rats, but the blood glucose level in the ZLC rats was only slightly
increased by 152.3 mg/dl. DCX immunoreactivity was significantly decreased in 12-week-old rats in comparison to 4-week-old
rats. Some DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in the ZLC rats. However,
only a few DCX-immunoreactive neurons were observed in the ZDF rats, and the DCX-immunoreactive neurons in the ZDF rats did
not show fully developed processes. These results suggest that DCX-immunoreactive neurons were significantly decreased in
an age-dependent manner and that DCX-immunoreactive neurons were also reduced in diabetic rats. In addition, the reduction
in DCX-immunoreactive neurons in age matched rats may be associated with type II diabetes. 相似文献
3.
Hwang IK Yi SS Yoo KY Park OK Yan B Song W Won MH Yoon YS Seong JK 《Neurochemical research》2011,36(2):281-287
Abnormal excess of glucocorticoid is one of feature characteristics in type 2 diabetes. In the present study, we investigated
the effect of treadmill exercise at chronic diabetic stages on glucocorticoid receptor (GR) immunoreactivity in the hippocampal
CA1 region and dentate gyrus, which are very vulnerable to diabetes. For this study, we used Zucker diabetic fatty (ZDF) rats
and Zucker lean control (ZLC) rats. Twenty-three-week-old ZLC and ZDF rats were put on the treadmill with or without running
for 7 weeks and sacrificed at 30 weeks of age. Treadmill exercise significantly decreased diabetes-induced blood glucose and
serum corticosteroid levels although they did not drop to control levels. In sedentary ZLC rats, GR immunoreactivity was detected
in pyramidal cells of the CA1 region as well as in granule cells of the dentate gyrus. In the sedentary ZDF rats, GR immunoreactivity
was significantly increased in these regions. However, treadmill exercise significantly decreased GR immunoreactivity in these
regions. These results indicate that treadmill exercise in chronic diabetic rats significantly decreased GR immunoreactivity
in the hippocampal CA1 region and dentate gyrus, although blood glucose and serum corticosteroid levels did not fully recover
to normal state. 相似文献
4.
Hwang IK Yi SS Yoo KY Park OK Yan B Song W Won MH Yoon YS Seong JK 《Neurochemical research》2011,36(8):1526-1532
In the present study, we investigated the effects of treadmill exercise in early and chronic diabetic stages on parvalbumin
(PV) immunoreactivity in the subgranular zone of the dentate gyrus of Zucker diabetic fatty (ZDF) and its lean control rats
(ZLC). To investigate the effects, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running
for 1 h/day/5 consecutive days at 16–22 m/min for 5 weeks or 12–16 m/min for 7 weeks, respectively. Physical exercise in pre-diabetic
rats prevented onset of diabetes, while exercise in rats at chronic diabetic stage significantly reduced blood glucose levels.
In addition, physical exercise in the pre-diabetic rats significantly increased PV immunoreactive fibers in the strata oriens
and radiatum of the CA1-3 region and in the polymorphic and molecular layers of the dentate gyrus compared to that in sedentary
controls. However, in rats at chronic stages, PV immunoreactivity was slightly increased in the CA1-3 region as well as in
the dentate gyrus compared to that in the sedentary controls. These results suggest that physical exercise has differential
effects on blood glucose levels and PV immunoreactivity according to diabetic stages. Early exercise improves diabetic phenotype
and PV immunoreactive fibers in the rat hippocampus. 相似文献
5.
Nam SM Kim YN Yoo DY Yi SS Kim W Hwang IK Seong JK Yoon YS 《Neurochemical research》2012,37(2):253-260
In this study, we investigated the differences in calbindin D-28k (CB), calretinin, (CR) and parvalbumin (PV) immunoreactivity
in the hippocampus of Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. In addition, we observed the effects
of hypothyroidism on the levels of immunoreactivity of these proteins in ZDF rats. For this study, 7-week-old ZDF rats were
used, and methimazole treatment was continued for 5 weeks to induce hypothyroidism. The animals were sacrificed at 12 weeks
of age. ZDF rats showed increased blood glucose levels compared to those in ZLC rats. Methimazole intervention significantly
reduced total and free T3 levels, and it ameliorated the increase of blood glucose levels in ZDF rats. In ZLC rats, CB, CR,
and PV immunoreactivity was detected in regions of the hippocampus proper. In vehicle-treated ZDF rats, CB, CR, and PV immunoreactivity
was significantly decreased in the hippocampus. However, in the methimazole-treated rats, CB, CR, and PV immunoreactivity
was significantly increased compared to that in the vehicle-treated rats. These results suggest that hypothyroidism ameliorated
the diabetes-induced reduction of CB, CR, and PV immunoreactivity in the hippocampus. 相似文献
6.
Yi SS Hwang IK Chun MS Kim YN Kim IY Lee IS Seong JK Yoon YS 《Neurochemical research》2009,34(5):851-858
Diabetes is a metabolic disorder that is associated with the dysregulation of a number of systems within the body. In the
present study, we investigated glucocorticoid receptor (GR) immunoreactivity and its protein levels in the paraventricular
nuclei of 4-, 12-, 20- and 30-week-old Zucker diabetic fatty (fa/fa, ZDF) and in Zucker lean control (fa/+ or +/+, ZLC) rats, because the progressive induction of diabetes is detectable in this model after 7 weeks of age and chronic diabetic
conditions are maintained after 12 weeks of age. GR immunoreactivity was detected in parvocellular paraventricular nuclei
and this and GR protein levels were exponentially increased according to the ages. In particular, GR immunoreactivities and
protein levels were markedly more increased in 30-week-old ZDF rats than in age-matched ZLC group and in younger ZDF group.
The present study suggests that GR immunoreactivity and its protein level is associated with a degenerative phenotype in the
hypothalamus of from 12-weeks old in the ZDF rat type II diabetes model. 相似文献
7.
In Koo Hwang Sun Shin Yi Jae Hoon Shin Ki-Yeon Yoo Jung Hoon Choi Choong Hyun Lee Je Kyung Seong Yeo Sung Yoon Jeong Ho Park Moo-Ho Won 《Neurochemical research》2010,35(3):465-472
In the present study, we observed the effects of cyclosporine A (CsA), an efficient immunosuppressant, on cell proliferation
and neuroblast differentiation in the subgranular zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using Ki67 and doublecortin
(DCX) immunohistochemical staining, respectively. At 8 weeks of age, vehicle (physiological saline) or CsA was daily administered
(40 mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last administration. CsA treatment did not show any
influences in neurons, astrocytes and microglia based on immunohistochemistry for its markers, respectively. However, in the
CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration, positive cells were found in the SZDG, not in the vehicle-treated
group. In the vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG, whereas in the CsA-treated group Ki67+ nuclei were scattered in the SZDG, showing no difference in cell numbers. Numbers of DCX+ neuroblasts with well-developed processes (tertiary dendrites) were much lower in the CsA-treated group than those in the
vehicle-treated group; however, numbers of DCX+ neuroblasts with secondary dendrites were similar in both the groups. These results suggest that CsA significantly reduces
dendritic outgrowth and complexity from neuroblasts in the SZDG without any affecting in neurons, astrocytes and microglia
in normal mice. 相似文献
8.
Yi SS Hwang IK Kim YN Kim IY Pak SI Lee IS Seong JK Yoon YS 《Neurochemical research》2008,33(5):833-841
Arginine vasopressin (AVP) is known to a neuropeptide that plays important roles in water conservation, sodium homeostasis,
and in the regulation of serum osmolality. Several studies have reported that the elevated AVP level is related with diabetes
mellitus as an acute or chronic stressor using type 1 diabetes mellitus animal models. However, it is unclear as to how the
immunoreactivity and protein level of AVP in the brain is regulated in animal models of type 2 diabetes mellitus. In the present
study, Zucker diabetic fatty (ZDF) rats were employed as a type 2 diabetes mellitus model and were compared with Zucker lean
control (ZLC) rats with respect to AVP protein expression. Furthermore, in order to verify the regulation of AVP expression
before and after the onset of diabetes mellitus, pre-diabetic rats (4 week-old) and obese-diabetic rats (12 week-old) were
used. Blood glucose levels and water consumption were also measured and the results showed significantly high in 12 week-old
ZDF than any other groups. AVP expression levels in the paraventricular nucleus and supraoptic nucleus were found to be significantly
higher in 12 week-old ZDF rats than in 12 week-old ZLC rats and than in 4 week-old rats by immunostaining and western blotting.
Enhanced expression of AVP in these animals may be associated with type 2 diabetes mellitus.
Special issue article in honor of George Fink. 相似文献
9.
Hee-Jae Kim Byunghun So Jun Seok Son Han Sol Song Seung Lyul Oh Je Kyung Seong Hoyoung Lee Wook Song 《Journal of Exercise Nutrition & Biochemistry》2015,19(4):281-288
[Purpose]
In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats.[Methods]
Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week).[Results]
After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle.[Conclusion]
Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes. 相似文献10.
Yo Na Kim Sangok Kim Il-Yong Kim Jae Hoon Shin Sooyoung Cho Sun Shin Yi Wan Kyu Kim Kyung-Sub Kim Sanghyuk Lee Je Kyung Seong 《PloS one》2013,8(7)
Gene expression changes have been associated with type 2 diabetes mellitus (T2DM); however, the alterations are not fully understood. We investigated the effects of anti-diabetic drugs on gene expression in Zucker diabetic fatty (ZDF) rats using oligonucleotide microarray technology to identify gene expression changes occurring in T2DM. Global gene expression in the pancreas, adipose tissue, skeletal muscle, and liver was profiled from Zucker lean control (ZLC) and anti-diabetic drug treated ZDF rats compared with those in ZDF rats. We showed that anti-diabetic drugs regulate the expression of a large number of genes. We provided a more integrated view of the diabetic changes by examining the gene expression networks. The resulting sub-networks allowed us to identify several biological processes that were significantly enriched by the anti-diabetic drug treatment, including oxidative phosphorylation (OXPHOS), systemic lupus erythematous, and the chemokine signaling pathway. Among them, we found that white adipose tissue from ZDF rats showed decreased expression of a set of OXPHOS genes that were normalized by rosiglitazone treatment accompanied by rescued blood glucose levels. In conclusion, we suggest that alterations in OXPHOS gene expression in white adipose tissue may play a role in the pathogenesis and drug mediated recovery of T2DM through a comprehensive gene expression network study after multi-drug treatment of ZDF rats. 相似文献
11.
Dong-Hee Kim Seok-Hwan Kim Won-Hee Kim Chae-Ryen Moon 《Journal of Exercise Nutrition & Biochemistry》2013,17(4):199-207
Sorts of abnormal state, obesity and inflammation are involved in a number of serious disease occurring and both of them became important research topics among molecular biologists. UCP-2 and TNF-α respectively reflecting obese and inflammatory status have often been used to evaluate the effects of independent variable, such as exercise, on them. Because exercise has shown its potent control on obesity and inflammation, it is necessary to determine if exercise is working via same bioindices. The purpose of this study was to determine the effects of different treadmill exercise intensities on UCP-2 of brown adipose tissue and TNF-α of soleus muscle during 8 weeks in Zucker rat. Zucker rats were divided into four groups (n = 7 in each group): control group, low intensity exercise group, moderate intensity exercise group and high intensity exercise group. Zucker rats of the exercise groups were made to run on a motorized treadmill for 30 minutes once a day during 8 weeks. Rats were sacrificed 24 hours after the last bout of exercise. Blood glucose in Zucker rats were measured by Gluco-Card Ⅱ. Brown adipose tissue were extracted to analyze the level of UCP-2 and TNF-α, respectively. UCP-2 and TNF-α were analyzed using the Western Blotting technique. Statistical techniques for data analysis were repeated measure ANOVA and one way ANOVA to determine the difference between groups, and for post hoc test was Duncan'' test. The 5% level of significance was utilized as the critical level for acceptance of hypotheses for the study. The following results were obtained from this study; UCP-2 protein expression of brown adipose tissue in Zucker rats were increased significantly following exercise of the low and moderate intensities compared to those of control group after 8 weeks. It was shown that TNF-α protein expression of soleus muscle in Zucker rats were decreased significantly following exercise of the low and moderate intensities compared to those of control group after 8 weeks. But no significant differences in levels of fasting glucose were shown between groups. The present data suggested that low and moderate intensities treadmill exercise may improve glycometabolism control and fat oxidation by up-regulating UCP-2 expression. In addition, we found low and moderate intensities reduce damages on skeletal muscle by down-regulation the TNF-α in Zucker rats. Thus, the low and moderate intensity exercise are appropriate for anti-obesity and inflammatory effects. 相似文献
12.
Moriguchi S.; Kato M.; Sakai K.; Yamamoto S.; Shimizu E. 《Journal of applied physiology》1998,84(1):311-317
Moriguchi, S., M. Kato, K. Sakai, S. Yamamoto, and E. Shimizu. Exercise training restores decreased cellular immune functions in obese Zucker rats. J. Appl.Physiol. 84(1): 311-317, 1998.This studyinvestigated whether exercise training had a beneficial effect on thedecreased mitogen response and improved a decreased expression ofglucose transporter 1 (GLUT-1) in splenocytes from obese Zucker rats.Experimental groups were lean and sedentary and exercise-trained obeseZucker rats. Exercise training, running on a motor-driven treadmill for5 days/wk for 40 wk, did not induce a significant decrease in bodyweight in obese Zucker rats. The plasma insulin concentration, showinga significant increase compared with lean Zucker rats, was unaffectedby exercise training. However, the plasma triglyceride concentration inobese Zucker rats was significantly depressed by exercise training,whereas it was still higher than that in lean Zucker rats. In addition,natural killer cell activity and concanavalin A-induced mitogenesis ofsplenic lymphocytes of obese Zucker rats were significantly restored. In these splenic lymphocytes, glucose uptake was significantly lowercompared with that in lean Zucker rats, which was also improved byexercise training. Although the expression of GLUT-1, the major glucosetransporter in immune cells, was depressed in splenic lymphocytes ofobese Zucker rats, exercise training induced a significant improvement.These results suggest that exercise training has a beneficial effect onthe decreased cellular immune functions in obese Zucker rats, which isassociated, in part, with the improvement in GLUT-1 expression. 相似文献
13.
Smith AC Mullen KL Junkin KA Nickerson J Chabowski A Bonen A Dyck DJ 《American journal of physiology. Endocrinology and metabolism》2007,293(1):E172-E181
Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 +/- 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats (P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-gamma coactivator-1alpha, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle. 相似文献
14.
Daisuke Ito Pengyu Cao Takaaki Kakihana Emiko Sato Chihiro Suda Yoshikazu Muroya Yoshiko Ogawa Gaizun Hu Tadashi Ishii Osamu Ito Masahiro Kohzuki Hideyasu Kiyomoto 《PloS one》2015,10(9)
Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine) and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01), while both eNOS and nNOS expression were upregulated by exercise (p<0.01). Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01) and α-oxoaldehydes (the precursors for advanced glycation end products) (p<0.01) in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and α-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity. 相似文献
15.
Choi JH Chung JY Yoo DY Hwang IK Yoo KY Lee CH Yan BC Ahn JO Youn HY Won MH 《Cellular and molecular neurobiology》2011,31(8):1271-1280
Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have
multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived
MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation
of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin
(DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma.
However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC
injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC
transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single
Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated
Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At
this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These
results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC
injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain. 相似文献
16.
Oltman CL Coppey LJ Gellett JS Davidson EP Lund DD Yorek MA 《American journal of physiology. Endocrinology and metabolism》2005,289(1):E113-E122
We have examined the progression of vascular and neural deficits in Zucker rats, Zucker diabetic fatty (ZDF) diabetic rats, and age-matched lean ZDF rats from 8 to 40 wk of age. Both the ZDF diabetic and Zucker rats were glucose intolerant at 8 wk of age. The Zucker rats did not become hyperglycemic but were hyperinsulinemic through 32 wk of age. All ZDF diabetic rats became hyperglycemic by 8 wk of age. Through their life span, serum free fatty acids and triglycerides levels were significantly higher in Zucker and ZDF diabetic rats compared with age-matched lean ZDF rats. After 24 and 28 wk of age, endoneurial blood flow was significantly decreased in ZDF diabetic and Zucker rats. Motor nerve conduction velocity was significantly decreased after 12-14 wk of age in ZDF diabetic rats and at 32 wk of age in Zucker rats. ACh-mediated vascular relaxation of epineurial arterioles of the sciatic nerve was impaired after 8-10 wk of age in ZDF diabetic rats and after approximately 16 wk of age in Zucker rats. In contrast, vascular relaxation mediated by calcitonin gene-related peptide was impaired significantly after 28 wk of age in ZDF diabetic rats but not impaired in Zucker rats up to 40 wk of age. Markers of oxidative stress were differentially elevated in ZDF diabetic rats and Zucker rats. These data indicate that vascular and neural dysfunction develops in both Zucker and ZDF diabetic rats but at different rates, which may be the result of hyperglycemia. 相似文献
17.
Kishor M. Wasan Verica Risovic Violet G. Yuen John H. McNeill 《Journal of trace elements in medicine and biology》2006,19(4):251-258
PURPOSE: Recently, our laboratory group has reported that rats with Type 1 diabetes have decreased plasma homocysteine and cysteine levels compared to non-diabetic controls and that organic vanadium treatment increased plasma homocysteine concentrations to non-diabetic concentrations. However, to date, no studies have been done investigating the effects of organic vanadium compounds on plasma homocysteine and its metabolites in Type 2 diabetic animal model. These studies examined the effect of organic vanadium compounds [bis(maltolato)oxovanadium(IV) and bis(ethylmaltolato)oxovanadium(IV); BMOV and BEOV] administered orally on plasma concentrations of homocysteine and its metabolites (cysteine and cysteinylglycine) in lean, Zucker fatty (ZF) and Zucker diabetic fatty (ZDF) rats. ZF rats are a model of pre-diabetic Type 2 diabetes characterized by hyperinsulinemia and normoglycemia. The ZDF rat is a model of Type 2 diabetes characterized by relative hypoinsulinemia and hyperglycemia. METHODS: Zucker lean and ZF rats received BMOV in the drinking water at a dose of 0.19 +/- 0.02 mmol/kg/day. Lean and ZDF rats received BEOV by oral gavage daily at dose of 0.1 mmol/kg. The treatment period for both studies was 21 days. At termination, animals were fasted overnight (approximately 16 h) and blood samples were collected by cardiac puncture for determination of plasma glucose, insulin and homocysteine levels. Plasma homocysteine and its metabolites levels were determined using high-pressure liquid chromatography. Plasma glucose was determined using a Glucose Analyzer 2. Plasma insulin levels were determined by radioimmunoassay. Plasma triglycerides were determined by an enzymatic assay methodology. RESULTS: ZF (n = 4) and ZDF (n = 10) rats had significantly lower plasma homocysteine as compared to their respective lean groups (ZF 0.78 +/- 0.1 micromol/L vs. Zucker lean 2.19 +/- 0.7 micromol/L; ZDF 1.71 +/- 0.2 micromol/L vs. Zucker lean 3.02 +/- 0.3 micromol/L; p < 0.05). BMOV treatment in ZF rats restored plasma homocysteine levels to those observed in lean untreated rats (ZF treated: 2.04 +/- 0.2 micromol/L; lean 2.19 +/- 0.7 micromol/L). There was a modest effect of BMOV treatment on plasma glucose levels in ZF rats. BEOV treatment significantly decreased the elevated plasma glucose levels in the ZDF rats (lean 7.9 +/- 0.1 mmol/L; lean + vanadium 7.7 +/- 0.2 mmol/L; ZDF 29.9 +/- 0.4 mmol/L; ZDF + vanadium 17.4 +/- 0.3 mmol/L, p < 0.05). Organic vanadium treatment reduced cysteine levels in both ZF and ZDF rats. No differences in total plasma cysteinylglycine concentrations were observed. CONCLUSION: Plasma homocysteine levels are significantly reduced in a pre-diabetic model of Type 2 diabetes, which was restored to lean levels upon vanadium treatment; however, this restoration of plasma homocysteine levels was not seen in ZDF Type 2 diabetic rats following vanadium treatment. In the latter case vanadium treatment may not have totally overcome the insulin resistance seen in these animals. 相似文献
18.
The objective of this study was to investigate the duration of biological effects of modified insulin glargine released from
a novel biodegradable injectable gel in type II diabetic Zucker diabetic fatty (ZDF) rats. Modified insulin glargine was purified
from the marketed formulation by process of dialysis followed by freeze-drying, and the purity was confirmed by the single
peak, corresponding to insulin glargine in the HPLC chromatogram. To determine and to compare the biological activity of purified
insulin glargine with marketed formulation, it was suspended in isotonic saline solutions and administered subcutaneously
to ZDF rats at a dose of 10 IU/kg of insulin and the blood glucose levels were measured. The blood glucose levels of ZDF rats
after a subcutaneous injection of a suspension of purified insulin glargine decreased below 200 mg/dL within 2 h and remained
at this level up to 6 h, then steadily raised above 400 mg/dL in 12 h. Insulin glargine particles were loaded into a novel
biodegradable injectable gel formulation prepared from a blend of polylactic-co-glycolic acid (PLGA) and biocompatible plasticizers.
Approximately 0.1 mL of insulin glargine-loaded gel prepared with PLGA was administered subcutaneously to the ZDF rats, and
blood glucose levels were measured. The PLGA gel formulations prepared with insulin glargine particles had duration of action
of 10 days following a single subcutaneous injection. The addition of zinc sulfate to the formulations prepared with purified
insulin glargine particles further slowed down the drop in blood glucose concentrations. 相似文献
19.
Jung Hoon Choi Ki-Yeon Yoo Choong Hyun Lee Ok Kyu Park Bing Chun Yan Hua Li In Koo Hwang Jeong Ho Park Sung Koo Kim Moo-Ho Won 《Neurochemical research》2010,35(10):1599-1608
In the present study, we investigated age-related differences in neuronal progenitors in the gerbil main olfactory bulb (MOB)
using doublecortin (DCX), a marker for neuronal progenitors which differentiate into neurons in the brain. No difference in
the number of neuronal nuclei (NeuN)-immunoreactive neurons was found in the MOB at variously aged gerbils. At postnatal month
(PM) 1, DCX immunoreaction was detected in all layers of the MOB except for the olfactory nerve layer. At this time point,
DCX-immunoreactive cells (neuronal progenitors) were very abundant; however, they did not have fully developed-processes.
From PM 3, the number of DCX-immunoreactive neuronal progenitors was decreased with age. At PM 6, DCX-immunoreactive cells
showed very well-developed processes. In western blot analysis, DCX protein level in the MOB was highest at PM 1. Thereafter,
levels of DCX protein were decreased with age. In the subventricular zone of the lateral ventricle, the number of Ki-67-immunoractive
cells (proliferating cells) was also significantly decreased with age. In addition, increases of α-synuclein-immunoreactive
structures were observed in the MOB with age. These results suggest that decrease in DCX-immunoreactive neuronal progenitors
and its protein levels in the MOB with age may be associated with reduction of cell proliferation in the SVZ and with an increase
in α-synuclein in the MOB. 相似文献
20.
Yoo DY Woo YJ Kim W Nam SM Lee BH Yeun GH Yoon YS Won MH Park JH Hwang IK 《Neurochemistry international》2011,59(5):722-728
In this study, we synthesized [1-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)pentan-1-one, HBU-39], a (α)-lipoic acid derivative, and found this compound strongly inhibited butyrylcholinesterase (BuChE) in an in vitro experiment. We also examined the effects of HBU-39 on cell proliferation and neuroblast differentiation using the specific markers Ki67 and doublecortin (DCX), respectively, in the hippocampal dentate gyrus of a rat model of scopolamine-induced amnesia. For this, scopolamine was subcutaneously administered for 28 days by an ALzet osmotic minipump (44 mg/mL delivered at 2.5 μL/h). HBU-39 (1 mg/kg per day) and galantamine (an acetylcholinesterase inhibitor used as a control; 5 mg/kg per day) were intraperitoneally administered for 28 days. The administration of scopolamine significantly decreased the mean number of Ki67- and DCX-immunoreactive cells in the dentate gyrus. However, treatment with both HBU-39 and galantamine significantly ameliorated the reductions in cell proliferation and neuroblast differentiation. In particular, the mean number of Ki67- and DCX-immunoreactive cells was prominently abundant in the HBU-treated group compared to that in the galantamine-treated group. These results suggest that the BuChE inhibitor, HBU-39, can ameliorate the scopolamine-induced reductions of cell proliferation and neuroblast differentiation, and HBU-39 may be applicable to amnesia patients to promote memory functions. 相似文献