Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

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.

Role of Alpha Lipoic acid on metabolic Hepatosteatosis: an experimental, biochemical, and microscopic study

Background and aim of work: metabolic hepatosteatosis is a common serious prevalent condition in KSA. The current study investigated alpha lipoic acid [ALA] effects on hepatic lipid accumulation in severely fatty rats and secondarily on blood lipid profile

Materials and methods: sixty male Zucker rats were selectively used half of which [Lean] weighed 200 +/- 25g and others weighed 375 +/- 30g. Fatty animals were allowed free access to food and water for one week before experiment. The animals were divided into lean untreated [group I], lean ALA - managed [group II], fatty untreated [group III] and fatty ALA managed [group IV] [fifteen animals per each group]. ALA was taken orally [20 mg/kg/day] for six months. Animals were sacrificed and weighed [BW]. Their liver was weighed [LW] and its portion was sliced to study its lipid content. Right tibia length [TL] was measured and LW: TL ratio was calculated

Results: ZF ALA-untreated rats showed high LW: TL ratio. ALA therapy significantly reduced BW, TL, LW and LW: TL ratio in managed ZF rats compared to untreated ones while it didn't affect these parameters significantly in lean [ZL] rats. ZF rats exhibited significant hepatosteatosis evidenced by excessive liver triglyceride [TG] and total cholesterol [TC] contents and microscopically by large cytoplasmic vacuoles. Interestingly, 6-months' ALA therapy in ZF caused significantly diminished serum triglycerides and cholesterol levels as well as diminished hepatic triglycerides and TC component in addition to decreased its lipid vacuoles compared to untreated ZF rats. The results were insignificantly changed between managed and untreated lean groups

Conclusion: our findings support effectiveness of ALA therapy in excessive hepatosteatosis and in hyperlipidemia via improving abnormal lipid metabolism

The Preventive Effects of 8 Weeks of Resistance Training on Glucose Tolerance and Muscle Fiber Type Composition in Zucker Rats

BACKGROUND: We investigated the therapeutic effects of resistance training on Zucker rats before and after the onset of diabetes to understand the importance of the timing of exercise intervention. We assessed whether 8 weeks of resistance training ameliorated impaired glucose tolerance and altered muscle fiber type composition in Zucker rats. METHODS: Five-week-old male Zucker rats were divided into Zucker lean control (ZLC-Con), non-exercised Zucker diabetic fatty (ZDF-Con), and exercised Zucker diabetic fatty (ZDF-Ex) groups. The ZDF-Ex rats climbed a ladder three times a week for 8 weeks. Intraperitoneal glucose tolerance tests (IPGTT) were performed on the 1st and 8th weeks of training, and grip strength was measured during the last week. We also measured glucose transporter 4 (GLUT4) expression by Western blot and immunofluorescence. Moreover, immunohistochemistry was performed to assess muscle fiber type composition. RESULTS: Fasting glucose levels and area under the curve responses to IPGTTs gradually increased as diabetes progressed in the ZDF-Con rats but decreased in the ZDF-Ex rats. Grip strength decreased in the ZDF-Con rats. However, resistance training did not improve grip strength in the ZDF-Ex rats. GLUT4 expression in the ZLC-Con and the ZDF-Con rats did not differ, but it increased in the ZDF-Ex rats. The proportions of myosin heavy chain I and II were lower and higher, respectively, in the ZDF-Con rats compared to the ZLC-Con rats. Muscle fiber type composition did not change in the ZDF-Ex rats. CONCLUSION: Our results suggest that regular resistance training initiated at the onset of diabetes can improve glucose tolerance and GLUT4 expression without changing muscle morphology in Zucker rats.

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.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.

Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats

BACKGROUND: Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models. METHODS: Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles. RESULTS: After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04). CONCLUSION: The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

Effect of Treadmill Exercise on Interleukin-15 Expression and Glucose Tolerance in Zucker Diabetic Fatty Rats

BACKGROUND: Interleukin-15 (IL-15), a well-known myokine, is highly expressed in skeletal muscle and is involved in muscle-fat crosstalk. Recently, a role of skeletal muscle-derived IL-15 in the improvement of glucose homeostasis and insulin sensitivity has been proposed. However, little is known regarding the influence of endurance training on IL-15 expression in type 2 diabetic skeletal muscles. We investigated the effect of endurance exercise training on glucose tolerance and IL-15 expression in skeletal muscles using type 2 diabetic animal models. METHODS: Male Zucker diabetic fatty (ZDF) and ZDF lean control (ZLC) rats were randomly divided into three groups: sedentary ZLC, sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). The ZDF-Ex rats were forced to run a motor-driven treadmill for 60 minutes once a day 5 times per week for 12 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed after 12 weeks. Expression of IL-15 was measured using ELISA in extracted soleus (SOL) and gastrocnemius medial muscles. RESULTS: After 12 weeks of treadmill training, reduction of body weight was observed in ZDF-Ex compared to ZDF-Con rats. Glucose tolerance using IPGTT in diabetic rats was significantly improved in ZDF-Ex rats. Furthermore, the expression of IL-15 was significantly increased (P<0.01) only in the SOL of ZDF-Ex rats compared to ZDF-Con. Additionally, IL-15 expression in SOL muscles was negatively correlated with change of body weight (R=-0.424, P=0.04). CONCLUSION: The present study results suggest that 12 weeks of progressive endurance training significantly improved glucose tolerance with concomitant increase of IL-15 expression in SOL muscles of type 2 diabetic rats.

Treinamento físico aeróbio previne à hipertrofia cardíaca patológica e melhora a função diastólica em ratos Zucker obesos / Aerobic exercise training revert pathologic cardiac hypertrophy and improves the diastolic function in obese Zucker rats

A obesidade é uma patologia diretamente relacionada com o desenvolvimento de doenças cardiovasculares. Por outro lado, o treinamento físico aeróbio atenua o desenvolvimento da obesidade e promove benefícios cardíacos em obesos. Dessa forma, nosso objetivo foi investigar se a obesidade altera a função cardíaca e se sua associação com o treinamento físico aeróbio promove melhora na função cardíaca em ratos Zucker obesos. Os ratos Zucker foram divididos da seguinte forma: grupo magro (GM), grupo obeso (GO), grupo magro treinado (GMTR) e grupo obeso treinado (GOTR). O protocolo de treinamento aeróbio de natação foi realizado por um período de 10 semanas com cinco sessões semanais de 60 minutos de duração. A frequência cardíaca de repouso, a pressão arterial sistólica, a hipertrofia e função cardíaca foram avaliadas no final do período de treinamento físico. Ambos os grupos treinados apresentaram uma queda de 12 por cento da frequência cardíaca de repouso, quando comparado com seus respectivos controles. Ainda, nossos resultados demonstraram que o treinamento aeróbio reduziu o aumento da massa cardíaca em 13 por cento e melhorou a função diastólica na obesidade em 43 por cento. Em conclusão, nossos dados demonstraram que o treinamento físico aeróbio reverteu os prejuízos cardíacos causados pela obesidade.

Obesity is profoundly involved in cardiovascular diseases. On the other hand, aerobic exercise training (EXT) attenuates obesity and promotes cardiac benefits in obese individuals. Therefore, the aim of this study was to investigate if obesity alters the cardiac function and whether its association with exercise training can improve cardiac function in an obese Zucker rat strain. The rats were divided in the following groups: Lean Zucker rats (LZR); lean Zucker rats plus exercise training (LZR+EXT); obese Zucker rat (OZR) and obese Zucker rat plus exercise training (OZR+EXT). EXT consisted of 10 weeks swimming sessions of 60 min, 5 days/week. At the end of the training protocol we evaluated heart rate (HR), systolic blood pressure (SBP), cardiac hypertrophy (CH) and function. The trained groups LZR+EXT and OZR+EXT showed a 12 percent lower resting HR when compared with theirs respective controls. In addition, our results showed that exercise training reduced the cardiac mass by 13 percent and improved the diastolic function by 43 percent in the obese trained group when compared with the obese untrained. In conclusion, aerobic exercise training reverts the cardiac injuries in obese Zucker rats.

Quantitative evaluation of experimental choroidal neovascularization by confocal scanning laser ophthalmoscopy: fluorescein angiogram parallels heparan sulfate proteoglycan expression

The objective of the present study was to develop a quantitative method to evaluate laser-induced choroidal neovascularization (CNV) in a rat model using Heidelberg Retina Angiograph 2 (HRA2) imaging. The expression of two heparan sulfate proteoglycans (HSPG) related to inflammation and angiogenesis was also investigated. CNV lesions were induced with argon laser in 21 heterozygous Zucker rats and after three weeks a fluorescein angiogram and autofluorescence exams were performed using HRA2. The area and greatest linear dimension were measured by two observers not aware of the protocol. Bland-Altman plots showed agreement between the observers, suggesting that the technique was reproducible. After fluorescein angiogram, HSPG (perlecan and syndecan-4) were analyzed by real-time RT-PCR and immunohistochemistry. There was a significant increase in the expression of perlecan and syndecan-4 (P < 0.0001) in retinas bearing CNV lesions compared to control retinas. The expression of these two HSPG increased with increasing CNV area. Immunohistochemistry demonstrated that the rat retina damaged with laser shots presented increased expression of perlecan and syndecan-4. Moreover, we observed that the overexpression occurred in the outer layer of the retina, which is related to choroidal damage. It was possible to develop a standardized quantitative method to evaluate CNV in a rat model using HRA2. In addition, we presented data indicating that the expression of HSPG parallels the area of CNV lesion. The understanding of these events offers opportunities for studies of new therapeutic interventions targeting these HSPG.

tepary bean diet and exercise delays indices of type 2 diabetes in female fa/fa rats

Legumes have been shown to protect against the development of type 2 diabetes [T2D]. Previous work has focused on the impact of legumes on the glycemic index with little attention given to other physiological changes. Considerable evidence also demonstrates that exercise is beneficial for diabetic individuals. This study sought to determine the individual and synergistic effects of a legume diet and exercise on indices of T2D and tested the hypothesis that the synergy of these factors would protect against typical changes in glycemic hormones and lipids across the weight gain and insulin resistant stage of development in genetically obese rats. Fatty Zucker [fa/fa] rats, 6-7 wks of age were assigned to one of four treatment groups [n = 10/group]; 1] tepary bean diet and exercise [TE], 2] tepary bean diet [T], 3] control diet and exercise [CE], 4] control diet [C]. A legume diet and exercise [TE] resulted in significantly less weight gain [126 g vs. 222 g in [C]] and lower body mass compared to animals in other treatment groups. The interaction of [TE] also resulted in significantly lower serum insulin compared to [C] animals across the study period. Diet [T] alone, significantly decreased serum triglycerides and cholesterol relative to [C] animals. Our results indicate that a tepary bean diet, with exercise, can decrease typical changes in weight gain, glycemia and lipid profile in fa/fa rats. The adoption of such a program in individuals showing signs of T2D would also likely serve to protect against these physiological changes

Effect of Rhodiola Sachalinensis Administration and Endurance Exercise on Insulin Sensitivity and Expression of Proteins Related with Glucose Transport in Skeletal Muscle of Obese Zucker Rat

Peripheral insulin resistance in obese/type II diabetes animals results from an impairment of insulin-stimulated glucose uptake into skeletal muscle. Insulin stimulate the translocation of GLUT4 from intracellular location to the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) is implicated in mediation of fusion of GLUT4-containing vesicle with the plasma membrane. Present study investigated regulatory effects of Rhodiola sachalinensis administration and exercise training on the expression of GLUT4 protein and SNAREs protein in skeletal muscles of obese Zucker rats. Experimental animals were randomly assigned into one of five groups ; lean control (LN), obese control (OB), exercise-treated (EXE), Rhodiola sachalinensis-treated (Rho), combine of Rho & EXE (Rho-EXE). All animals of exercise training (EXE, Rho-EXE) performed treadmill running for 8 weeks, and animals of Rho groups (Rho, Rho-EXE) were dosed daily by gastric gavage during the same period. After experiment, blood were taken for analyses of glucose, insulin, and lipids levels. Mitochondrial oxidative enzyme (citrate synthase, CS ; beta-hydroxyacyl-CoA dehydrogenase, beta-HAD) activity were analysed. Skeletal muscles were dissected out for analyses of proteins (GLUT4, VAMP2, syntaxin4, SNAP23). Results are as follows. Exercise and/or Rhodiola sachalinensis administration significantly reduced body weight and improved blood lipids (TG, FFA), and increased insulin sensitivity. Endurance exercise significantly increased the activity of mitochondrial enzymes and the expression of GLUT4 protein, however, administration of Rhodiola sachalinensis did not affect them. The effect of exercise and/or Rhodiola sachalinensis administration on the expression of SNARE proteins was unclear. Our study suggested that improvement insulin sensitivity by exercise and/or Rhodiola sachalinensis administration in obese Zucker rats is independent of expression of SNARE proteins.

Envolvimento do óxido nítrico e da serotonina hipotalâmica no efeito da interleucina-1beta sobre a ingestão alimentar em ratos Zucker normais e obesos / Involvement of nitric oxide and hipothalamic serotonin on the effect of interlekin-1beta on food intake in normal and obese Zucker rats

A anorexia induzida por serotonina (5-HT) faz parte de um importante mecanismo central de controle do balanço energético. Recentente foi sugerido interleucina-lbeta (IL-lbeta) e óxido nítrico (NO) podem participar do controle da homeostase energética, possivelmente através da modulação do sistema serotoninérgico hipotalâmico. Este trabalho foi realizado para investigar interações entre estes sistemas. Através de microdiálise, observamos que a influenciada durante anorexia induzida por IL-1beta em ratos Zucker obesos e magros. Demonstramos que a administração intracerebroventricular de 10 ng de IL-1beta estimulou significantemente a liberação de 5-HT no hipotálamo ventromedial (VMH), com um pico de variação de 102 ± 41 por cento nos obesos e de 130 ± 39 por cento nos magros. Observamos efeito anorexígeno significante na ingestão de 4h e 24h após tratamento com IL-1beta. A ingestão aguda de 4 h foi reduzida em 29 por cento nos magros e em 33 por cento nos obesos, enquanto a ingestão de 24 h foi reduzida em 58 por cento nos magros e em 44 por cento nos obesos. O pré-tratamento i.c.v.com 20 g do precursor do NO L-arginina, bloqueou a liberação de 5-HT estimulada pela IL-beta. Este pré-tratamento aboliu o efeito anorexígeno da IL-beta somente nos animais obesos, sugerindo que a ativação do sistema serotoninérgico no VMH foi essencial para a anorexia induzida por IL-beta. Sugere-se que, nos animais obesos, a perda de um sinal anorexígeno, devido ao bloqueio da liberação de 5-HT após pré-tratamento com L-arg, foi determinante para reverter anorexia causada por IL. Já nos magros, nos quais o sistema hipotalâmico de controle da ingestão está íntegro, provavelmente o bloqueio de um único sistema anorexígeno (5-HT) foi compensado pela ativação de outros e/ou inibição de fatores orexígenos

A Micropncture Study on Renal Function and Hemodynamic Factors in Obese Rats / 대한신장학회잡지

It has been commonly noted that male patients have worse prognosis in adult polycystic kidney disease, IgA nephropathy, and membranous nephropathy. Several animal experiments were performed to clarify the mechanisms by which male gender confers a more adverse renal prognosis. Obese Zucker rats are characterized by severe obesity, insulin resistance, extremely high serum insulin level, high cholesterol level and spontaneous glomerular sclerosis. The aim of current study was to investigate whether there was a gender difference in 1) mean arterial pressure and renal function 2) glomerular volume by renal perfusion 3) glomerular hemodynamic factors including glomerular blood flow, glomerular pressure, renal vascular resistance, ultrafiltration coefficient by micropuncture techniques in obese male and female Zucker rats. There was no difference in blood glucose, serum insulin level, mean arterial pressure and glomerular sclerosis rate between male and female Zucker rats. Male Zucker rats had slightly higher glomerular filtration rate, kidney weight, single nephron glomerular filtration rate, glomerular capillary hydraulic pressure which was statistically insignificant. These findings suggest that gender difference in hemodynamic factors does not play a role in the progression of renal disease in obese Zucker rats.