共查询到20条相似文献,搜索用时 15 毫秒
1.
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
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.
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
4.
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
5.
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
6.
Yi SS Hwang IK Yoo KY Park OK Yu J Yan B Kim IY Kim YN Pai T Song W Lee IS Won MH Seong JK Yoon YS 《Neurochemical research》2009,34(6):1039-1046
In the present study, we investigated the effects of a treadmill exercise on serum glucose levels and Ki67 and doublecortin
(DCX) immunoreactivity, which is a marker of cell proliferation expressed during cell cycles except G0 and early G1 and a
marker of progenitors differentiating into neurons, respectively, in the subgranular zone of the dentate gyrus (SZDG) using
a type II diabetic model. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a
treadmill with or without running for 1 h/day/5 consecutive days at 22 m/min for 5 weeks. Body weight was significantly increased
in the control (without running)-ZDF rats compared to that in the other groups. In the control groups blood glucose levels
were increased by 392.7 mg/dl in the control-ZDF rats and by 143.3 mg/dl in the control-ZLC rats. However, in the exercise
groups, blood glucose levels were similar between the exercise-ZLC and ZDF rats: The blood glucose levels were 110.0 and 118.2 mg/dl,
respectively. Ki67 positive nuclei were detected in the SZDG in control and exercise groups. The number of Ki67 positive nuclei
was significantly high in exercise groups compared to that in the control groups. In addition, Ki67 positive cells were abundant
in ZLC groups compared to those in ZDF groups. DCX-immunoreactive structures in the control-ZDF rats were lower than that
in the control-ZLC rats. In the exercise groups, DCX-immunoreactive structures (somata and processes with tertiary dendrites)
and DCX protein levels were markedly increased in both the exercise-ZLC and ZDF rats compared to that in the control groups.
These results suggest that a treadmill exercise reduces blood glucose levels in ZDF rats and increases cell proliferation
and differentiation in the SZDG in ZLC and ZDF rats compared to those in control groups. 相似文献
7.
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
8.
Complement inhibition reduces injury in the type 2 diabetic heart following ischemia and reperfusion
La Bonte LR Davis-Gorman G Stahl GL McDonagh PF 《American journal of physiology. Heart and circulatory physiology》2008,294(3):H1282-H1290
Chronic inflammation exacerbates the cardiovascular complications of diabetes. Complement activation plays an important role in the inflammatory response and is known to be involved in ischemia-reperfusion (I/R) injury in the nondiabetic heart. The purpose of this study was to determine if increased complement deposition explains, in part, the increased severity of neutrophil-mediated I/R injury in the type 2 diabetic heart. Nondiabetic Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats underwent 30 min of coronary artery occlusion followed by 120 min of reperfusion. Another group of ZDF rats was treated with the complement inhibitor FUT-175 before reperfusion. Left ventricular (LV) tissue samples were stained for complement deposition and neutrophil accumulation following reperfusion. We found significantly more complement deposition in the ZDF LV compared with the ZLC (P < 0.05), and complement deposition was associated with significantly greater neutrophil accumulation. In whole blood samples taken preischemia and at 120 min reperfusion, neutrophils exhibited significantly more CD11b expression in the ZDF group compared with the ZLC group (P < 0.05). Furthermore, intracellular adhesion molecule (ICAM)-1 expression following I/R was increased significantly in ZDF hearts compared with ZLC hearts (P < 0.001). These results indicate that, in the ZDF heart, increased ICAM-1 and polymorphonuclear neutrophil (PMN) CD11b expression play a role in increasing PMN accumulation following I/R. The infarct size of the ZDF was significantly greater than ZLC (P < 0.05), and treatment with FUT-175 significantly decreased infarct size, complement deposition, and PMN accumulation in the diabetic heart. These findings indicate an exacerbated inflammatory response in the type 2 diabetic heart that contributes to the increased tissue injury observed following ischemia and reperfusion. 相似文献
9.
Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L~(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (10 mmol L~(-1)) and occasionally normal (0–10 mmol L~(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period. 相似文献
10.
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11.
Ji Yeon Kim Keun Jae Park Gyu Hee Kim Eun Ae Jeong Dae Yeon Lee Seong Su Lee Dae Jin Kim Gu Seob Roh Jihyun Song Sung Hwan Ki Won-Ho Kim 《Cellular signalling》2013,25(12):2348-2361
In obese Zucker diabetic fatty (ZDF) rats, ER stress is associated with insulin resistance and pancreatic β-cell dysfunction; however the exact mechanisms by which ER stress drives type-2 diabetes remain uncertain. Here, we investigated the role of ATF3 on the preventive regulation of AMPK against ER stress-mediated β-cell dysfunction during the end-stage progression of hyperglycemia in ZDF rats. The impaired glucose metabolism and β-cell dysfunction were significantly increased in late-diabetic phase 19-week-old ZDF rats. Although AMPK phosphorylation reduced in 6- and 12-week-old ZDF rats was remarkably increased at 19 weeks, the increases of lipogenice genes, ATF3, and ER stress or ROS-mediated β-cell dysfunction were still remained, which were attenuated by in vivo-injection of chemical chaperon tauroursodeoxycholate (TUDCA), chronic AICAR, or antioxidants. ATF3 did not directly affect AMPK phosphorylation, but counteracts the preventive effects of AMPK for high glucose-induced β-cell dysfunction. Moreover, knockdown of ATF3 by delivery of in vivo-jetPEI ATF3 siRNA attenuated ER stress-mediated β-cell dysfunction and enhanced the beneficial effect of AICAR. Our data suggest that ATF3 may play as a counteracting regulator of AMPK and thus promote β-cell dysfunction and the development of type-2 diabetes and could be a potential therapeutic target in treating type-2 diabetes. 相似文献
12.
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
13.
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
14.
Litherland Gary J. Hajduch Eric Gould Gwyn W. Hundal Harinder S. 《Molecular and cellular biochemistry》2004,261(1):23-33
Fructose is a major dietary sugar, which is elevated in the serum of diabetic humans, and is associated with metabolic syndromes important in the pathogenesis of diabetic complications. The facilitative fructose transporter, GLUT5, is expressed in insulin-sensitive tissues (skeletal muscle and adipocytes) of humans and rodents, where it mediates the uptake of substantial quantities of dietary fructose, but little is known about its regulation. We found that GLUT5 abundance and activity were compromised severely during obesity and insulin resistance in Zucker rat adipocytes. Adipocytes from young obese (fa/fa), highly insulin-responsive Zucker rats contained considerably more plasma membrane GLUT5 than those from their lean counterparts (1.8-fold per microgram membrane protein), and consequently exhibited higher fructose transport (fivefold) and metabolism (threefold) rates. Lactate production was the preferred route for fructose metabolism in these cells. As the rats aged and become more obese and insulin-resistant, adipocyte GLUT5 surface density (12-fold) and fructose transport (10-fold) and utilisation rates (threefold) fell markedly. The GLUT5 loss was more dramatic in adipocytes from obese animals, which developed a more marked insulin resistance than lean counterparts. The decline of GLUT5 levels in adipocytes from older, obese animals was not a generalised effect, and was not observed in kidney, nor was this expression pattern shared by the 1 subunit of the Na+/K+ ATPase. Our findings suggest that plasma membrane GLUT5 levels and thus fructose utilisation rates in adipocytes are dependent upon cellular insulin sensitivity, inferring a possible role for GLUT5 in the elevated circulating fructose observed during diabetes, and associated pathological complications. (Mol Cell Biochem 261: 23–33, 2004) 相似文献
15.
Brain Insulin-Like Growth Factor-II mRNA Content Is Reduced in Insulin-Dependent and Non-Insulin-Dependent Diabetes Mellitus 总被引:1,自引:0,他引:1
Laura Wuarin Ritu Namdev J. Gregory Burns Zhi-Jian Fei Douglas N. Ishii 《Journal of neurochemistry》1996,67(2):742-751
Abstract: Diabetic encephalopathy, characterized by structural, electrophysiological, neurochemical, and cognitive abnormalities, is observed in insulin-dependent diabetes mellitus (IDDM) and non-IDDM (NIDDM). Identification of early biochemical lesions potentially may provide clues pointing to its pathogenesis. Insulin-like growth factors (IGFs) are neurotrophic factors that recently have been implicated in the pathogenesis of diabetic neuropathy. Because IGF-II is the predominant IGF in adult brain, we tested the hypothesis that IGF-II gene expression is decreased in the CNS in both IDDM and NIDDM. Brain and spinal cord were isolated from streptozotocin-diabetic rats, a model of IDDM with weight loss and impaired insulin production. IGF-II mRNA content was measured by northern and slot blots. After 2 weeks of diabetes, IGF-II mRNA content per milligram of tissue wet weight, as well as per unit of poly(A)+ RNA, declined significantly (p≤ 0.05) in brain and spinal cord. Insulin replacement therapy partially restored IGF-II mRNA levels in brain, cortex, medulla, and spinal cord. The obese, hyperinsulinemic, and spontaneously diabetic (fa/fa) Zucker rat was used as a model of NIDDM. Brain weight (p < 0.025) and IGF-II mRNA contents (p < 0.01) were significantly decreased in (fa/fa) versus lean nondiabetic (+/?) rats. Therefore, the decline in IGF-II mRNA levels in diabetic brain was independent of the type of diabetes, the direction of change in body weight, and the insulinemic state. We speculate that this early biochemical lesion may contribute to the development of diabetic encephalopathy. 相似文献
16.
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
17.
Halina Staniek Nicholas R. Rhodes Kristin R. Di Bona Ge Deng Sharifa T. Love Leigh Ann Pledger Jeremy Blount Emmalea Gomberg Frances Grappe Chelsea Cernosek Brittany Peoples Jane F. Rasco Zbigniew Krejpcio John B. Vincent 《Biological trace element research》2013,151(3):373-383
Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)3]) (1 mg?Cr/kg body mass), CrCl3 (1 mg?Cr/kg body mass), and Cr3 ([Cr3O(propionate)6(H2O)3]+) (33 μg and 1 mg?Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl3 and Cr3, but not [Cr(pic)3], at 1 mg?Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes. 相似文献
18.
Christof Burgdorf Laura Hänsel Marc Heidbreder Frank Schütte Thomas Kurz 《Biochemical and biophysical research communications》2009,390(1):165-59
Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP1) activity. Here, we studied cardiac PAP1 activity and lipin expression ex vivo in 8-month-old Zucker diabetic fatty (ZDF) rats and humans with type 2 diabetes mellitus undergoing open heart surgery for coronary bypass grafting. Compared to non-diabetic littermates (ZDF-fa/+), left ventricular PAP1 activity was 29% lower in diabetic ZDF-fa/fa rats. Left ventricular PAP1 activities were 2.1-fold (ZDF-fa/fa) and 3.6-fold (ZDF-fa/+) higher than the respective atrial activities, indicating marked differences in cardiac distribution of PAP1. PAP1 activity was highly related with cardiac lipin-1 and lipin-3 mRNA expression in ZDF rats (r = 0.99 and 0.96). Consistent with the findings in experimental animals, human atrial tissue displayed PAP1 activity that was 33% lower in those having diabetes than in non-diabetic controls. Accordingly, atrial lipin-1 and lipin-3 mRNA expression in diabetic patients was 50% and 59% lower as in non-diabetic patients, respectively. Insulin therapy increased both PAP1 activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP1 activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart. 相似文献
19.
Arantza Gutirrez Gonzalo Saracíbar Luis Casis Enrique Echevarría Víctor Manuel Rodríguez Maria Teresa Macarulla Luis C. Abecia María P. Portillo 《Obesity (Silver Spring, Md.)》2002,10(6):532-540
Objective: The aim of this work was to study the potential involvement of neuropeptide Y (NPY) and orexins in the anorexigenic mechanism of fluoxetine in obese Zucker rats, assessing the effects of chronic fluoxetine treatment on NPY and orexin immunostaining in several hypothalamic regions. Research Methods and Procedures: Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg intraperitoneally) daily for 2 weeks. The control group was administered 0.9% NaCl solution. Carcass composition was assessed using the official methods of the Association of Official Analytical Chemists. To test the potential thermogenic effect of fluoxetine administration, total body oxygen consumption was measured daily for 60 minutes before fluoxetine or saline injection and for 30 minutes after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei, and the lateral hypothalamic area were immunostained for NPY, orexin A, and orexin B. Commercial kits were used for serum determinations. Results: Chronic fluoxetine administration in obese Zucker rats generated a reduction in body weight gain, food intake, adipocyte size, fat mass, and body protein. A decrease in NPY immunostaining in the paraventricular nucleus, without changes in the arcuate, was observed. However, no changes were observed in the number of neural cells immunostained for orexin A or orexin B in the lateral hypothalamic area. Discussion: Due to the hyperphagic effect of NPY in the paraventricular nucleus, these results suggest that NPY, but not orexins, could be involved in the anorexigenic effect of fluoxetine in obese Zucker rats. 相似文献
20.
Impact of Type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart 总被引:1,自引:0,他引:1
Fülöp N Mason MM Dutta K Wang P Davidoff AJ Marchase RB Chatham JC 《American journal of physiology. Cell physiology》2007,292(4):C1370-C1378
Increased levels of O-linked attachment of N-acetylglucosamine (O-GlcNAc) on nucleocytoplasmic proteins are implicated in the development of diabetic cardiomyopathy and are regulated by O-GlcNAc transferase (OGT) expression and its substrate UDP-GlcNAc. Therefore, the goal of this study was to determine whether the development of diabetes in the Zucker diabetic fatty (ZDF) rat, a model of Type 2 diabetes, results in defects in cardiomyocyte mechanical function and, if so, whether this is associated with increased levels of O-GlcNAc and increased OGT expression. Six-week-old ZDF rats were hyperinsulinemic but normoglycemic, and there were no differences in cardiomyocyte mechanical function, UDP-GlcNAc, O-GlcNAc, or OGT compared with age-matched lean control rats. Cardiomyocytes isolated from 22-wk-old hyperglycemic ZDF rats exhibited significantly impaired relaxation, compared with both age-matched lean control and 6-wk-old ZDF groups. There was also a significant increase in O-GlcNAc levels in high-molecular-mass proteins in the 22-wk-old ZDF group compared with age-matched lean control and 6-wk-old ZDF groups; this was associated with increased UDP-GlcNAc levels but not increased OGT expression. Surprisingly, there was a significant decrease in overall O-GlcNAc levels between 6 and 22 wk of age in lean, ZDF, and Sprague-Dawley rats that was associated with decreased OGT expression. These results support the notion that an increase in O-GlcNAc on specific proteins may contribute to impaired cardiomyocyte function in diabetes. However, this study also indicates that in the heart the level of O-GlcNAc on proteins appears to be differentially regulated by age and diabetes. hexosamine biosynthesis; protein O-glycosylation; O-linked N-acetylglucosamine transferase 相似文献