Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.     

Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in a model of type 2 diabetes

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.     

Electroacupuncture at the Zusanli and Baihui acupoints ameliorates type-2 diabetes-induced reductions in proliferating cells and differentiated neuroblasts in the hippocampal dentate gyrus with increasing brain-derived neurotrophic factor levels

In the current study, we investigated whether electroacupuncture (EA) can inhibit pathological reductions in neurogenesis. Zucker diabetic fatty (ZDF) rats at 7 weeks of age were anesthetized with zoletil, and sham-acupuncture or EA at the Zusanli (ST36) and Baihui (GV20) acupoints was administered once a day for 5 weeks. In the ZDF group that received sham-EA (ZDF-Sham group), the blood glucose level was significantly increased together with age as compared to the control littermates [Zucker lean control (ZLC) rat]. In contrast, proliferating cells and differentiated neuroblasts were significantly decreased in the ZDF-Sham group compared to the ZLC group. Although EA treatment decreased blood glucose levels, this was not statistically significant when compared to blood glucose levels changes in the ZDF-Sham group. However, proliferating cells and differentiated neuroblasts were significantly increased with EA in ZDF rats as compared to those in the ZDF-Sham group. Brain-derived neurotrophic factor (BDNF) levels were significantly decreased in hippocampal homogenates of ZDF-Sham group compared to those in the ZLC group. The EA treatment significantly increased the BDNF levels compared to those in the ZDF-Sham group, and BDNF levels in this group were similar to those in the ZLC group. These results suggest that EA at ST36 and GV20 can ameliorate the reductions in proliferating cells and differentiated neuroblasts in the dentate gyrus induced by type-2 diabetes without significantly reducing blood glucose levels with increasing BDNF levels.     

Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis

In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our re sults demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations.     

Changes in orexin-A and neuropeptide y expression in the hypothalamus of obese and lean Zucker Diabetic Fatty rats

This study was carried out to investigate the changes of orexin-A (OXA) and neuropeptide Y (NPY) expression in the hypothalamus of the obese and lean Zucker Diabetic Fatty (ZDF) rats which have a missense mutation in the leptin receptor gene. The mean body weights (MBW) between the obese and lean ZDF rats were significantly different at 28 and 70 postnatal days. However, at 14 postnatal day, there was no significant difference in the MBW between the obese and lean ZDF rats in both male and female. The OXA immunoreactivities were not significantly different between the obese and lean ZDF rats in both sexes at 14, 28, and 70 postnatal days, respectively. The NPY immunoreactivity was higher in the obese than in the lean ZDF rats in both male and female at 28 and 70 postnatal days, whereas there was no significant difference between the obese and lean ZDF rats at 14 postnatal day. These results indicate that both OXA and NPY might halt their roles for food intake in the obese phenotype of the male and female ZDF rats in the preweaning period of 14 postnatal day, whereas NPY might play a main role in the obesity of these rats in the weaning period of 28 and 70 postnatal days.     

Changes in cyclooxygenase-2 immunoreactivity in the hippocampus in a model of streptozotocin-induced type 1 diabetic rats

In this study, we investigated diabetic stage dependent cyclooxygenase-2 (COX-2) immunoreactivity in the dentate gyrus in streptozotocin (STZ)-induced type 1 diabetic rats. The animals were sacrificed at 2, 3 and 4 weeks after STZ treatment. Blood glucose levels were increased after STZ treatment. COX-2 immunoreactivity in dentate gyrus was significantly increased in these regions 3 weeks after STZ treatment and restored to its basal level to 4 weeks after STZ treatment. In contrast, COX-2 immunoreactivity was not changed in CA3 region in all groups. These results suggest that STZ-induced type 1 diabetes transiently, but not permanently, decreased synaptic transmission and plasticity 3 weeks after STZ treatment in the dentate gyrus.     

Endocrine cell populations in the pancreas of diabetic WBN/Kob rats.

Numerical changes of insulin-, glucagon- and somatostatin-positive cells in the pancreas of WBN/Kob male rats with spontaneously occurring diabetes were examined. The rats examined were divided into three different age groups: Groups I (12 weeks old) and II (33 weeks old) were clinically prediabetic and group III (60-90 weeks old) was diabetic. Serum glucose value was in the normal range in groups I and II, while it was much higher in group III. B and A cells were markedly decreased in number in groups II and III. In group II, the ratio of B to A cells was normally preserved, though the total endocrine cell number was markedly decreased as compared with that in group I. In group III, the percentage of B cells was decreased significantly. The normal ratio in group II seemed to keep serum glucose within the normal level. In addition to the total endocrine cell reduction, an altered ratio of B and A cells was considered to cause the diabetic condition.     

Morphoquantitative aspects of NADH-diaphorase myenteric neurons in the ileum of diabetic rats treated with acetyl-L-carnitine

In this work, we investigated the effect of the acetyl-L-carnitine (ALC) supplementation (200 mg/kg/day) on the myenteric neurons of the ileum of rats made diabetic by streptozotocin (35 mg/kg, i.v.). Four groups were used: diabetic (D), diabetic supplemented with ALC (DC), control (C) and control supplemented with ALC (CC). After 15 weeks of diabetes induction the animals were killed and the ileum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The density of neurons seen in 12.72 mm2 of ileum showed no difference among the groups, although in group D it was 22% smaller than in group C, while group DC was 9% smaller to group CC. The profiles of the cell bodies (PC) of 1000 neurons per group were analysed. The neurons PC in group D decreased (P < 0.0001) when compared with other groups and increased (P < 0.0001) when compared with group DC. The incidence of neurons with a PC inferior to 200 microm2 was larger in group D. The frequency of neurons with a PC higher than 200 microm2 in group DC was close to those seen in groups C and CC. We concluded that ALC eases the loss of neurons and makes the incidence of myenteric neurons with a PC higher than 200 microm2 similar to the control rats.     

Age-related changes in calretinin-immunoreactive periglomerular cells in the rat main olfactory bulb

The changes of calretinin (CR)-immunoreactive periglomerular cells in the glomerular layer of the main olfactory bulb (MOB) were investigated in rats differing ages from postnatal month 1 (PM 1) to PM 24. The number of cresyl violet-positive periglomerular cells was similar between PM 1 and PM 12, but they decreased slightly in the PM 24 group. The size of CR-immunoreactive periglomerular cells in the glomerular layer increased with age, while their numbers did not change significantly in the PM 6-PM 24 groups. In the PM 24 group, numbers of CR-positive periglomerular cell bodies and their processes decreased, while the size of CR-positive cell bodies in the glomeruli was larger than that of the previous groups. These results suggest that CR-immunoreactive periglomerular cells in the rat MOB are well-developed in the PM 6 group, and that periglomerular cells in the PM 24 group show poor CR-immunoreactivity compared to those in the PM 6 group.     

Time-dependent changes of calbindin D-28K and parvalbumin immunoreactivity in the hippocampus of rats with streptozotocin-induced type 1 diabetes

The hippocampus is affected by various stimuli that include hyperglycemia, depression, and ischemia. Calcium-binding proteins (CaBPs) have protective roles in the response to such stimuli. However, little is known about the expression of CaBPs under diabetic conditions. This study was conducted to examine alterations in the physiological parameters with type 1 diabetes induced with streptozotocin (STZ) as well as time-dependent changes in the expression of two CaBPs changes of were being evaluated. Rats treated with STZ (70 mg/kg) had high blood glucose levels (>21.4 mmol/L) along with increased food intake and water consumption volumes compared to the sham controls. In contrast, body weight of the animals treated with STZ was significantly reduced compared to the sham group. CB-specific immunoreactivity was generally increased in the hippocampal CA1 region and granule cell layer of the dentate gyrus (DG) 2 weeks after STZ treatment, but decreased thereafter in these regions. In contrast, the number of PV-immunoreactive neurons and fibers was unchanged in the hippocampus and DG 2 weeks after STZ treatment. However, this number subsequently decreased over time. These results suggest that CB and PV expression is lowest 3 weeks after STZ administration, and these deficits lead to disturbances in calcium homeostasis.     

Effects of exercise during the growing-finishing period on performance, age at puberty and conception rate of gilts

Littermate gilts were used to study the effects of exercise during the growing-finishing period on performance, age at puberty and conception rate. In trial 1, 12 gilts walked 15 min daily on a treadmill 6 d/wk (Monday through Saturday) until they attained body weights of about 100 kg, while 12 littermate gilts were not forced to exercise. Initial weight and age averaged 24.7 kg and 74 d, respectively. For trial 2, 12 gilts walked 30 min daily 6 d/wk (Monday through Saturday) on a treadmill, while 12 littermate gilts were not exercised. Initial weight and age of these gilts averaged 26.8 kg and 76 d, respectively. The treadmill was operated at 0 slope and at a speed of 2.6 km/h. Within trial, there were no differences (P greater than .05) in weight gain, average daily gain, feed consumed, feed to gain ratio, average backfat depth of loin eye area between gilts exercised and those not exercised. In both trials, there were no differences (P greater than .05) in age at puberty between exercised and nonexercised gilts. In trial 2, 10 gilts were selected in each of the exercised and nonexercised groups and were hand-mated to the same boar on the second estrous cycle. Eight gilts from the exercised group conceived, while nine from the nonexercised group conceived. Four gilts from the nonexercised groups had severe locomotor problems while only one gilt from the exercised groups had difficulty walking.     

Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-L-carnitine

The NADPH-diaphorase (NADPH-d) positive myoenteric neurons from the body of the stomach of rats with streptozotocin-induced diabetes with or without supplementation with acetyl-L-carnitine (ALC) were evaluated. At the age of 105 days the animals were divided into four groups: normoglycaemic (C), normoglycaemic supplemented with ALC (CC), diabetic (D) and diabetic supplemented with ALC (DC). The supplementation with ALC (200 mg/kg body weight/day) to groups CC and DC was made during 105 days. After this period the animals were killed and the stomach removed and subjected to the histochemical technique of NADPH-d for the staining of the neurons of the myoenteric plexus. The area of 500 neurons of each group was investigated, as well as the neuronal density in an area of 23.84 mm(2) in each stomach. ALC promoted reduction (P < 0.05) of fasting glycaemia, water ingestion and areas of the profiles of the cell bodies of the NADPH-d neurons in the diabetic animals. The density of these neurons was not statistically different in the groups studied. It is suggested, therefore, a moderate neuroprotective effect of ALC, because the diminishment of the areas of the neuronal profiles in the supplemented diabetic animals, although being statistically significant relative to the non-supplemented diabetics, was not sufficient to equal the values from the non-diabetic controls.     

Effects of eight weeks of physical conditioning on atherosclerotic plaque in swine

Effects of individually prescribed exercise on the regression or interference with deposition of atherosclerotic plaque were studied. Twenty miniature swine allotted, by litter, to a control-diet group (groups CE and CS) and an atherogenic diet group (groups AE and AS). All pigs were subjected to injury (balloon catheter) of the aortic endothelium. They were fed for 8 weeks and after an initial graded exercise test was done, then each group was suballotted to an exercising group (groups CE and AE) or a sedentary group (groups CS and AS). Groups CE and AE (exercised) were given 8 weeks of training. Groups CS and AS (sedentary) were sham exercised during this period. A second graded exercise test was administered to the swine (all groups) before they were euthanatized. Aortas were analyzed for the percentage of area involved and for atherosclerotic plaque density. Samples of blood from the swine after they were fasted were obtained before the start of the project (base line) and once every 2 weeks thereafter. These were analyzed for triglycerides, high- and low-density lipoprotein, and total cholesterol concentration. Comparison of results of blood lipid analyses from weeks 1, 9, and 15 did not show significant differences within diet groups between exercise and sedentary. Significant differences at weeks 9 and 15 were observed between diet groups (ie, the pigs fed the atherosclerotic diet had higher blood lipids). Plaque formation was not found in the pigs fed the control diet (groups CE and CS). Plaque formation was evident in all pigs fed the atherosclerotic diet (groups AE and AS) with no significant differences between exercised and sedentary groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous thyroiditis in BB Wistar diabetic rats

Spontaneous lymphocytic thyroiditis was observed at necropsy in 36 BB Wistar diabetic rats (63.2%) and in eight of their nondiabetic siblings (42.1%). The incidence of thyroiditis decreased both with age and with longer duration of diabetes. All rats with pancreatic insulitis (a manifestation of the onset of diabetes) also had thyroiditis. BB Wistar rats with insulitis had more severe lymphocytic thyroiditis, characterized by lymphocytic, plasmacytic, and macrophage infiltration of thyroid interstitium and follicles. A milder, mostly perivascular and interstitial lymphocytic thyroiditis was characteristic of lesions in rats which did not have insulitis. The histological appearance of the thyroiditis suggests that these rats may be subject to autoimmune disease at the onset of diabetes which involves sites other than just the pancreas.     

硒对STZ诱发糖尿病大鼠骨密度影响的研究初报

比较了在低硒饲料的基础上补充不同形态硒对糖尿病大鼠骨密度的影响。健康SD大鼠 1 2 8只 ,体重 50～ 60 g,随机分为 4组 ,每组 32只 ,雌雄各半 ,其中Ⅰ组为低硒对照组 (饲料含硒量 0 0 37mg/kg) ;Ⅱ组为补充亚硒酸钠组 (饲料含硒量 0 3mg/kg) ;Ⅲ组为补充富硒麦芽组(饲料含硒量 0 3mg/kg) ;Ⅳ组为补充富硒酵母组 (饲料含硒量 0 3mg/kg)。Ⅱ、Ⅲ、Ⅳ组的饲料均是在Ⅰ组低硒饲料的基础上分别添加适量的亚硒酸钠、富硒麦芽、富硒酵母后配制而成。喂饲 5周后 ,Ⅰ、Ⅱ、Ⅲ、Ⅳ组用链脲佐菌素 (streptozotocin ,STZ)按 60mg/kg腹腔注射诱发糖尿病 ,继续饲喂 6周。用单光子吸收法测定各组大鼠的肱骨、股骨、胫骨、桡骨的骨密度。结果表明 :①STZ致糖尿病大鼠的骨密度随时间的延长有逐渐下降的趋势。Ⅱ、Ⅲ、Ⅳ补硒组大鼠可以在一定时间内延缓STZ致糖尿病大鼠的骨密度下降。在此期间骨密度的下降以肱骨出现最早 ,股骨次之 ,桡骨、胫骨再次之。②饲料补硒组糖尿病大鼠的肱骨、股骨中硒的含量较饲料低硒组糖尿病大鼠的肱骨、股骨中硒的含量显著提高。③补充硒的形态 ,即有机硒 (富硒麦芽、富硒酵母 )或无机硒 (亚硒酸钠 )对糖尿病大鼠肱骨、股骨、胫骨、桡骨的骨密度影响差异不显著。     

Training-induced alterations of the fatty acid profile of rabbit muscles

The present study was designed to investigate whether meat-type rabbits are able to perform treadmill running as a daily routine exercise, and if so, whether the exercise induces specific proportional changes in the fatty acid composition of their muscles. After a four-week training period 8-week-old rabbits were slaughtered and the total activity of plasma lactate dehydrogenase was measured, showing a significant difference between the exercised and control groups (429 +/- 126 IU/l vs. 639 +/- 203 IU/l). Furthermore the fatty acid composition of m. longissimus dorsi (MLD) and m. vastus lateralis (MVL) was determined by means of gas chromatography. Exercise increased the proportions of oleic acid (C18:1 n-9) in both MLD and MVL as compared to the control group. However, the level of stearic (C18:0) and arachidonic (C20:4 n-6) acids significantly decreased in the MVL after the exercise. Changes in the fatty acid profile resulting from the physically loaded condition were of the same tendency in both muscles, adding that the MVL might have been exposed to the exercise more intensively; alterations there occurred in a more pronounced manner. Based on the inference that the composition of membrane structure was also affected, these alterations may have important consequences on meat quality.     

Effect of prolonged branched-chain amino acid supplementation on metabolic response to anaerobic exercise in standardbreds

This study investigated the effect of prolonged BCAA supplementation on metabolic response to a 1600m run on treadmill in Standardbred trotters. Four trained Standardbreds were divided into two groups and assigned in a 2×2 Latin square design. Both groups were fed and exercised similarly: one group received an oral amino acids supplement (12 g leucine, 9 g isoleucine and 9 g valine) 30 minutes prior to exercise and immediately after, the other group received a placebo. The horses received the supplement 3 days per week for 5 weeks. In the last week horses performed an anaerobic exercise test on an inclined (3.5%) high-speed treadmill. The exercise consisted of a 15 minute warm-up phase immediately followed by a 1600 m run at maximal speed (heart rate > 200 beats/min). Blood samples were collected pre-exercise, after exercise and during recovery (10 min, 30 min, and 24 h), and analyzed for lactate, ammonia, total protein, urea, uric acid, creatinine, free fatty acids (FFA), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate amino transferase (AST). Heart rate was continuously recorded during exercise and recovery. No statistical differences between the groups were observed for all the considered parameters. Nevertheless, BCAA supplementation resulted in a higher plasma ammonia and urea concentrations as reported in previous studies in humans and rats. These data suggest that a BCAA supplementation are not effective in enhancing performance in healthy and well-fed horses.     

Effects of treadmill exercise on cortical bone in the third metacarpus of young horses.

The effects of exercise and relative inactivity on cortical bone were compared in young horses. Two groups were used; one was given a 14-week programme of exercise (n = 6) and the other kept as unexercised controls (n = 6). The first nine weeks of exercise involved trotting and cantering (2 to 4 km d-1 at speeds up to 12 m s-1) on a treadmill set at an incline of 3 degrees. Over the next five weeks the horses were trained at near maximal speeds (that is, up to 14.5 m s-1) with no incline of the treadmill. At the end of the programme marked differences in cortical porosity and distribution of subperiosteal osteogenesis at the mid-shaft of the third metacarpal bone were found between the groups. Histomorphometrical examination of the dorsal cortex showed minimal bone remodelling in the exercised horses, but extensive modelling as evidenced by the large amount of subperiosteal bone formation. In contrast, the unexercised horses had significantly more bone remodelling and less formation of subperiosteal bone. The histomorphometric and microradiographic findings provided an explanation for changes in the non-invasive bone measurements that occurred during training. Bone mineral content of the mid-metacarpus was found to increase more in the exercised than the unexercised horses despite a lower overall growth in bodyweight. In those horses that completed the full training programme, ultrasound speed increased significantly by the end of the training programme. It remained unchanged in the horse that did not complete the full exercise programme and decreased slightly in the unexercised horses. The difference in ultrasound speed between the groups was considered to reflect differences in intracortical bone porosity, endosteal bone formation and alterations in skin thickness. The stiffness of cortical bone increased significantly in the exercised horses but remained unaltered in the unexercised horses.     

Morphological changes in the sciatic nerve of diabetic rats treated with low molecular weight heparin OP 2123/parnaparin

This study points out the early alterations that affect the sciatic nerve of rats with experimentally induced diabetes. It emphasizes the advantages deriving from treatment with low molecular weight heparin (LMWH) OP 2123/parnaparin and correlates these findings with observations emerging from a review of the relevant literature. In fact, the number and diameter of the capillaries within the sciatic nerve of diabetic rats appear to be increased consistent with a microangiopathy (the main characteristic of which is the fragility of new vessels), that is related to the evolution of diabetes in humans and animals. Our results suggest a possible therapeutic role for OP 2123/parnaparin in both diabetic neuropathy and microangiopathy, frequent complications of diabetes.     

Evaluation of serum concentrations of biochemical markers of bone metabolism and insulin-like growth factor I associated with treadmill exercise in young horses

OBJECTIVE: To evaluate changes in serum concentrations of biochemical markers of bone metabolism and insulin-like growth factor I (IGF-I) associated with treadmill exercise in young horses. ANIMALS: 12 two-year-old Thoroughbred mares. PROCEDURE: During a 20-week study period, 6 horses were exercised on a treadmill 3 times a week (exercise group) and 6 horses received walking exercise 6 days a week (controls). Serum concentrations or activity of biochemical markers and IGF-I were assessed biweekly. Bone mineral density and content of the first phalanx were measured by dual-energy X-ray absorbiometry (DEXA) on completion of the study. RESULTS: Compared with values in controls, bone mineral density and content were higher and serum concentrations of osteocalcin (a marker of bone formation) and the carboxy-terminal telopeptide of type I collagen (a marker of bone resorption; ICTP) were lower in exercised horses. Serum concentration and activity of the bone formation markers carboxy-terminal propeptide of type I collagen and bone-specific alkaline phosphatase (BAP) were not different between the 2 groups. Serum IGF-I concentration was lower in the exercise group, compared with control values; there was a significant correlation between change in IGF-I values and changes in osteocalcin, ICTP, and BAP values at the end of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Treadmill exercise over 20 weeks induced adaptive changes in bones of 2-year-old Thoroughbreds; training appears to increase bone mineral density, thereby enhancing mechanical strength of bone, but decreases bone turnover. Results indicated an association between changes in serum IGF-I concentration and bone cell activity in horses.