Effects of long-term inhibition of neuronal nitric oxide synthase (NOS1) in uninephrectomized diabetic rats.

Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic changes in diabetes mellitus (DM). However, the role of NO in the pathophysiology of diabetic nephropathy remains controversial. Renal hemodynamic changes in experimental DM can be acutely normalized by selective inhibition of neuronal NO synthase (nNOS). This observation suggests a nephroprotective potential of nNOS inhibition in DM. To explore this issue we assessed the long-term effects (12 weeks) of selective nNOS inhibition with the specific inhibitor S-methyl-L-thiocitrulline (SMTC) in uninephrectomized control and streptozotocin-diabetic rats. No beneficial effects of SMTC were observed in nondiabetic controls. In contrast, SMTC delayed the development of proteinuria (32+/-8 vs. 53+/-9 mg/24h, week 8, p < 0.05) and glomerulosclerosis (GS, 0.30+/-0.08 vs. 0.57+/-0.05, p < 0.05) in diabetic rats. These effects coincided with early effects of treatment on the glomerular filtration rate, and were associated with lower renal expression of nNOS. Furthermore, SMTC-treated diabetic rats demonstrated reduced weight gain and urinary sodium excretion as compared to vehicle-treated counterparts, despite similar metabolic control and blood pressure. In summary, long-term nNOS inhibition had modest nephroprotective effects in uninephrectomized diabetic rats. These effects may be mediated by renal hemodynamic mechanisms, as well as by lower food (protein) intake.     

Enzymes of myo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes.

Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy.     

The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes

In this present study, the duration of melatonin (Mel) administered to diabetic rats was prolonged so as to examine its effects on the biochemical liver parameters of diabetic rats. In the experiment, Male Sprague Dawley rats were divided randomly into five groups; the control, diabetic + Mel, diabetic, diabetic + insulin, and diabetic + Mel + insulin. Diabetes mellitus was induced by administration of a single dose of streptozotocin (60 mg/kg) intraperitoneally and rats were given vehicle as a solvent for Mel every day for 12 weeks. In the diabetic + Mel group, diabetic rats were administered Mel (10 mg/kg/day) for 12 weeks to treat diabetes. The diabetic + insulin group were diabetic rats given insulin (6 U/kg) subcutaneously for 12 weeks. The diabetic + Mel + insulin rats received insulin and Mel at the same dose and time. At the end of the experiment, the animals were decapitated and liver tissues were taken. The protective effect of Mel on liver tissue of diabetic rats was investigated, total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, adenosine deaminase, xanthine oxidase, paraoxonase 1, sodium/potassium ATPase, myeloperoxidase, γ-glutamyl transferase, sorbitol dehydrogenase, tumor necrosis factor-alpha, homocysteine, nitric oxide, glucose-6-phosphate dehydrogenase, and glycoprotein levels were determined in liver tissues. Treatment with Mel and/or insulin has been found to have a protective effect on biochemical parameters. The results showed that administration of Mel to diabetic rats prevented the distortion of the studied biochemical parameters of liver tissues.     

Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.     

人脐带间充质干细胞移植对糖尿病大鼠血清学的影响

目的:观察人脐带间充质干细胞(hu MSCs)移植对糖尿病大鼠血糖、胰岛素和血清因子表达的影响。方法:随机选择12只Wistar大鼠通过腹腔注射链脲佐菌素50 mg/kg,血糖高于16.7 mmol/L者定为糖尿病大鼠,再将其随机分为糖尿病组和干细胞组,每组6只,同时选择6只雄性Wistar大鼠为正常组。干细胞组大鼠腹腔注射hu MSCs细胞悬液,糖尿病组注射PBS液。分别于注射2周、4周和6周后测定和比较各组大鼠的血糖、血清胰岛素、肿瘤坏死因子(TNF-α)和白介素-6(IL-6)的表达。结果:与正常组比较,糖尿病组和干细胞组大鼠的血糖水平均显著升高,胰岛素水平均显著降低(P0.01)。与糖尿病组比较,干细胞组大鼠注射hu MSCs后的血糖水平明显降低,胰岛素水平明显升高(P0.05),血清TNF-α和IL-6 m RNA水平均显著降低(P0.01)。结论:hu MSCs移植能显著降低糖尿病大鼠的血糖,促进其胰岛素分泌,同时降低血清TNF-α和IL-6的表达。     

In vivo effect of methylcobalamin on the peripheral nerve structure in streptozotocin diabetic rats

To study in vivo effect of methylcobalamin (CH3-B12) on the peripheral nerve structures, rats with experimental diabetes induced by streptozotocin were administered with daily intramuscular injection of CH3-B12 (500 microgram/kg) for 16 weeks. By isolated nerve fiber studies, CH3-B12-treated diabetic rats showed less incidence of paranodal demyelination as an early sign of segmental demyelination than non-treated diabetic rats. From morphometrical analysis on sural nerves, the reduction in the density of myelinated nerve fibers, nerve fiber size and axon size of myelinated fibers was definitely protected in treated diabetic rats. The results suggested that continuous treatment with CH3-B12 had an ameliorative effect on the peripheral nerve lesions in experimental diabetic neuropathy.     

The Diabetic Nephropathy and the Development of Hypertension in Rats

The present study was designed to examine the development of hypertension in diabetic rats treated with streptozotocin (STZ, 1mg/g bw). The rats were studied at 3, 6, 9, 12 and 15 weeks. From the third week the rats were divided in diabetic rats according their glycemias and controls, along 15 weeks. After the third week a group, of rats showed increased urinary protein excretion (93, 134, 155 and 191%) compared to controls. In this group of rats the urinary kallikrein excretion was lower than control and the systolic blood pressure became significantly elevated between 3 and 6 weeks and persisted up to 15 weeks. On the other hand a group of diabetic rats were normotensive with urinary protein excretion similar to controls and urinary kallikrein lower compared to control but significantly higher compared diabetic hypertensive rats. These data suggest that the association of progressive diabetic nephropathy with abnormal endothelium-dependent vasodilation may produce a high prevalence of hypertensive diabetes.     

Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats

Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n?=?128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n?=?54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n?=?64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.     

Effect of diabetes on calcium/calmodulin dependent protein kinase-II from rat brain.

Changes in the protein levels and activity of Ca2+/Calmodulin dependent protein kinase II (CaM kinase II) level were studied in cytosolic and particulate fractions from cerebral hemisphere, cerebellum, brain stem, thalamus and hypothalamus regions of rat brain after 4 and 12 weeks of induction of diabetes. Streptozotocin induced diabetes, resulted in pronounced increase of CaM kinase II activity as determined by the kinase activity assay. The total amount of enzyme protein (alpha-subunit specific) also showed increase as revealed by western blotting. Parallel studies were also made in age matched control rats and insulin treated diabetic rats. The increase in CaM kinase II activity was more pronounced in the 12 weeks diabetic group. Insulin treatment of diabetic rats, resulted in recovery of enzyme activity near to control values from majority of the brain regions studied. The expression of alpha-subunit specific CaM kinase II correlates with the enzyme activity in the diabetic rat brain.     

Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats

Salvia miltiorrhiza (Sm) administration has been shown to reduce hepatic fibrosis in rats. We investigated the hemodynamic effects of Sm on bile duct ligated (BDL) rats. Hemodynamic, histological, and vascular contractile studies were conducted in rats 4 weeks after bile duct ligation. An aqueous extract of Sm (0.2 g twice per day) or vehicle was administered for 4 weeks to BDL rats. Sm treatment in BDL rats significantly reduced histological grades of fibrosis and ameliorated the portal hypertensive state (including portal venous pressure, superior mesenteric artery blood flow, cardiac index, and total peripheral resistance) as compared with vehicle treatment. Moreover, Sm treatment enhanced the vascular sensitivity of mesenteric arteries to phenylephrine in BDL rats. Sm treatment had no effect on plasma biochemical profiles of either BDL or normal rats. Our results suggest that 4-week Sm treatment ameliorates the portal hypertensive state in BDL rats.     

糖尿病大鼠外周神经山梨醇通路和Na^＋—K^＋—ATP酶活性的变化

本文用四氧嘧啶诱导产生糖尿病动物模型,分别于糖尿病产生后第4,8,12周测定大鼠坐骨神经匀浆山梨醇通路活性,肌醇含量和哇巴因敏感的和不敏感的 ATP 酶活性。与同龄正常对照组比较,糖尿病发生4周后,坐骨神经葡萄糖含量增加3—4倍,果糖增加3—5倍,山梨醇增加6—9倍,肌醇含量降低到对照组的50%,总 ATP 酶和哇巴因敏感的Na~+-K~+-ATP 酶活性均极显著地低于同龄对照组(P<0.01)。结果提示这些代谢变化可能是糖尿病神经病变发病机制中的重要环节。     

Impairment of transneuronal traffic in Streptozotocin-induced diabetes, a WGA-HRP neurohistochemical study in the rat

Retrograde transport of Wheat germ agglutinin conjugated to Horseradish peroxidase (WGA-HRP) was used in labeling vagal neurons projecting to the stomach from the dorsal motor nucleus of the vagus nerve (DMNV) in Streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in the experimental rats by intraperitoneal injection of buffered STZ. Control rats were injected with an equivalent volume of the citrate buffer not containing STZ. The experimental rats, which became diabetic about 24 h after intraperitoneal injection of STZ, were kept alive for a period of 24 weeks to attain a chronic state of diabetes. Control euglycaemic rats were also kept alive for 24 weeks. At the end of 24 weeks, the two groups of rats were prepared for stomach surgery. Following anaesthesia laparotomy was performed and the stomach exteriorized. The anterior and posterior walls of the stomach were injected with 0.1 ml of 5% WGA-HRP in 0.5 M sodium chloride. Experimental and control rats were sacrificed 48–72 h after tracer injection by transcardial perfusion with normal saline, fixative and buffered sucrose. Transverse serial frozen sections of the brainstem were processed for WGA-HRP neurohistochemistry and analyzed under light and dark-field microscopy. The analyses of the sections taken from the chronic diabetic rats revealed fewer WGA-HRP labeled neurons in the DMNV than sections taken from the control euglycaemic rats. The depletion of labeled neurons in the diabetic rats compared with the euglycaemic rats is indicative of an interference with the mechanism of retrograde neuronal transport of WGA-HRP by chronic diabetic state.     

Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications

Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used. One lean (Fa/?) and one obese (fa/fa) untreated group served as non-diabetic and diabetic controls. In two further groups of obese (fa/fa) rats, diabetes was prevented by pioglitazone or delayed by food restriction. All rats were monitored up to 35 weeks of age with respect to their blood glucose, HbA1c and insulin levels, their kidney function (urinary glucose excretion, renal glucose filtration, glomerular filtration rate, albumin/creatinine ratio), and their nerve function (tactile and thermal sensory threshold and nerve conduction velocity). Pioglitazone prevented the development of diabetes, while food restriction delayed its onset for 8-10 weeks. Accordingly, kidney function parameters were similar to lean non-diabetic rats in pioglitazone-treated rats and significantly improved in food-restricted rats compared with obese controls. Kidney histology paralleled the functional results. By contrast, nerve functional evaluations did not mirror the differing blood glucose levels. We conclude that the ZDF rat is a good model for diabetic nephropathy, while alterations in nerve functions were not diabetes-related.     

The effects of zofenopril on cardiac function and pro-oxidative parameters in the streptozotocin-induced diabetic rat heart

Diabetes mellitus is a chronic condition that continues to increase in both incidence and prevalence. Renin–Angiotensin–Aldosterone System is one of the main modulators of chronic hyperglycaemia and, thus, its influence on tissues. Hyperglycaemia-induced oxidative stress is an important factor in diabetic cardiomyopathy. The present study was carried out on 24 adult male Wistar albino rats (8-week-old and with body masses of 190 ± 10 g). We evaluated the influence of acute administration of zofenopril on ex vivo myocardial function from rats with streptozotocin-induced diabetes mellitus, with a special emphasis on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats were divided randomly into two groups (12 animals per group): control non-diabetic animals (C) were healthy rats perfused with 1.5 µM of zofenopril, and STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 µM of zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that diabetic rats are characterized by a depressed cardiac performance and that oxidative markers are related to alterations in cardiac function in rats with 4 weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia. However, long-term follow-up intervention trials are necessary to fully demonstrate the benefit of zofenopril in this context. A challenge for future investigations will be to identify the effects of chronic administration or combination therapy with angiotensin-converting enzyme inhibitors in various models of diabetes.     

Delayed remodeling in the early period of fracture healing in spontaneously diabetic BB/OK rats depending on the diabetic metabolic state

Several clinical series, analyzing fracture healing in patients with insulin-dependent type 1 diabetes (IDDM) demonstrated significant incidence of delayed union, non-union, and pseudarthrosis. The purpose of this study was to examine the detailed histomorphometry and histology of bone formation and remodeling during fracture healing depending on the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in man. A standardized fracture model was chosen and based on blood-glucose values at the time of surgery (mg%), postoperative blood-glucose course (mg%) and postoperative insulin requirements (IU/kg), 100 spontaneously diabetic BB/OK rats were divided into groups with well-compensated (n=50, 167+/-77 mg%; 244+/-68 mg%; 1.8+/-1.9 IU/kg) or poorly compensated (n=50, 380+/-89 mg%; 415+/-80 mg%; 6.0+/-1.0 IU/kg) metabolic state. Fifty LEW.1A rats served as the normoglycemic controls (97+/-15 mg%). Ten animals from each group were killed 1, 2, 3, 4 and 6 weeks after fracture and specimens were processed undecalcified for quantitative histomorphometry and for qualitative light microscopy. In terms of bone histomorphometry, within the first four weeks after fracture, severe mineralization disorders occurred exclusively in the rats with poorly compensated diabetic metabolic states with a significantly decrease of all fluorochrome-based parameters of mineralization, apposition, formation and timing of mineralization in comparison to the spontaneously diabetic rats with well-compensated metabolic states and to the control rats. This was confirmed histologically. Early fracture healing in the spontaneously diabetic BB/OK rats is delayed exclusively in poorly compensated diabetic metabolic states, and 6 weeks after fracture, histomorphometrically significant deficits in the measured and dynamically calculated parameters remain. This study suggests that strictly controlled insulin treatment resulting in well-compensated diabetic metabolic states will ameliorate the impaired early mineralization and cell differentiation disorders of IDDM fracture healing.     

Biomechanical and morphometric properties of the arterial wall referenced to the zero-stress state in experimental diabetes

Morphometric and passive biomechanical properties were studied in isolated segments of the thoracic and abdominal aorta, left common carotid artery, left femoral artery and the left pulmonary artery in 20 non-diabetic and 28 streptozotocin (STZ)-induced diabetic rats. The diabetic and non-diabetic rats were divided into groups living 1, 4, 8, and 12 weeks after the induction of diabetes (n = 7 for each diabetic group) or sham injection (n = 5 for each group). The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. The vessel diameter and length were obtained from digitized images of the arterial segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state data. The zero-stress state was obtained by cutting vessel rings radially causing the rings to open up into a sector. Diabetes was associated with pronounced morphometric changes, e.g., wall thickness. With respect to the biomechanical data, the opening angle increased and reached a plateau in 4 weeks after which it decreased again (p < 0.05). The opening angle was smallest in the thoracic aorta and largest in the pulmonary artery. Furthermore, it was found that the circumferential stiffness of the arteries studied increased with the duration of diabetes. In the longitudinal direction significant differences were found 8 weeks after injection of STZ in all arteries except the pulmonary artery. In the 12 weeks group, the femoral artery was stiffest in the circumferential direction whereas the thoracic aorta was stiffest in the longitudinal direction. The accumulated serum glucose level correlated with the arterial wall thickness and elastic modulus (correlation coefficient between 0.56 and 0.81).     

Adaptations in Mitochondrial Function Parallel,but Fail to Rescue,the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats

Cross‐sectional human studies have associated mitochondrial dysfunction to type 2 diabetes. We chose Zucker diabetic fatty (ZDF) rats as a model of progressive insulin resistance to examine whether intrinsic mitochondrial defects are required for development of type 2 diabetes. Muscle mitochondrial function was examined in 6‐, 12‐, and 19‐week‐old ZDF (fa/fa) and fa/+ control rats (n = 8–10 per group) using respirometry with pyruvate, glutamate, and palmitoyl‐CoA as substrates. Six‐week‐old normoglycemic–hyperinsulinemic fa/fa rats had reduced mitochondrial fat oxidative capacity. Adenosine diphosphate (ADP)‐driven state 3 and carbonyl cyanide p‐trifluoromethoxyphenylhydrazone (FCCP)‐stimulated state uncoupled (state u) respiration on palmitoyl‐CoA were lower compared to controls (62.3 ± 9.5 vs. 119.1 ± 13.8 and 87.8 ± 13.3 vs. 141.9 ± 14.3 nmol O₂/mg/min.). Pyruvate oxidation in 6‐week‐old fa/fa rats was similar to controls. Remarkably, reduced fat oxidative capacity in 6‐week‐old fa/fa rats was compensated for by an adaptive increase in intrinsic mitochondrial function at week 12, which could not be maintained toward week 19 (140.9 ± 11.2 and 57.7 ± 9.8 nmol O₂/mg/min, weeks 12 and 19, respectively), whereas hyperglycemia had developed (13.5 ± 0.6 and 16.1 ± 0.3 mmol/l, weeks 12 and 19, respectively). This mitochondrial adaptation failed to rescue the progressive development of insulin resistance in fa/fa rats. The transition of prediabetes state toward advanced hyperglycemia and hyperinsulinemia was accompanied by a blunted increase in uncoupling protein‐3 (UCP3). Thus, in ZDF rats insulin resistance develops progressively in the absence of mitochondrial dysfunction. In fact, improved mitochondrial capacity in hyperinsulinemic hyperglycemic rats does not rescue the progression toward advanced stages of insulin resistance.     

Diabetes Alters Aromatase Enzyme Levels in Sciatic Nerve and Hippocampus Tissues of Rats

Diabetes mellitus (DM) is associated with increased risk of impaired cognitive function. Diabetic neuropathy is one of the most common and important complications of DM. Estrogens prevent neuronal loss in experimental models of neurodegeneration and accelerate nerve regeneration. Aromatase catalyzes the conversion of androgens to estrogens and expressed in a variety of tissues including neurons. Although insulin is known to regulate the activity of aromatase there is no study about the effects of diabetes on this enzyme. Present study was designed to investigate the effects of experimental diabetes on aromatase expression in nervous system. Gender-based differences were also investigated. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks sciatic nerve and hippocampus homogenates were prepared and evaluated for aromatase proteins. Aromatase expressions in sciatic nerves of both genders were decreased in 4 weeks of diabetes, but in 12 weeks the enzyme levels were increased in females and reached to control levels in male animals. Aromatase levels were not altered in hippocampus at 4 weeks but increased at 12 weeks in female diabetic rats. No significant differences were observed at enzyme levels of hippocampus in male diabetic rats. Insulin therapy prevented all diabetes-induced changes. In conclusion, these results indicated for the first time that, DM altered the expression of aromatase both in central and peripheral nervous systems. Peripheral nervous system is more vulnerable to damage than central nervous system in diabetes. These effects of diabetes differ with gender and compensatory neuroprotective mechanisms are more efficient in female rats.     

Exercise protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway in rats

To explore the protective effect of exercise training on the injury of myocardium tissues induced by streptozotocin (STZ) in diabetic rats and the relationship with endoplasmic reticulum stress (ERS), the male sprague-dawley (SD) rats were fed with high-fat and high-sugar diet for 4 weeks, followed by intraperitoneal injection of STZ, 40 mg/kg, to establish a diabetes model, and then 10 rats were randomly selected as diabetes mellitus (DM) controls and 20 eligible diabetic rats were randomized into two groups: low-intensity exercise training (n = 10) and high-intensity exercise training (n = 10). After 12 weeks of exercise training, rats were killed and serum samples were used to determine cardiac troponin-I (cTn-I). Myocardial tissues were sampled for morphological analysis to detect myocardial cell apoptosis, and to analyze protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12. Different intensities (low and high) significantly reduced serum cTn-I levels compared with the DCM group (p < 0.01), and significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Hematoxylin and eosin and Masson staining indicated that exercise training could attenuate myocardial apoptosis. Additionally, exercise training significantly reduced GRP78, CHOP, and cleaved caspase-12 protein expression in an intensity-dependent manner. These findings suggest that exercise appeared to ameliorate diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in diabetic rats.     

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p<0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p<0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p<0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p<0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.