Adipose Tissue Of Diabetic Rats Research Articles

High-Intensity Interval Training and Vitamin D3 Supplementation Decrease CCL-5 and CCR5 Expression In White Adipose Tissue of Diabetic Rats Fed with A High-Fat Diet and Streptozotocin.

The purpose of this study was to investigate the effects of 8 weeks of high-intensity interval training (HIIT) and vitamin D3 supplementation on Chemokine (C-C motif) Ligand 5 (CCL-5) and C-C motif chemokine receptor 5 (CCR5) in the white adipose tissue (WAT) of male rats with type 2 diabetes (T2DM). The experimental study involved 40 male Wistar rats divided into 5 groups (n=8). These groups were healthy control (HC), diabetic control (DC), diabetic+HIIT (DHIIT), diabetic+vitamin D3 (DD3), and diabetic+HIIT+vitamin D3 (DHIITD3). The rats completed 8 weeks of HIIT, consisting of 12 sessions lasting 1 minute each at an intensity of 90-95% of their maximum running speed. Additionally, the rats were administered a weekly dose of 10,000 IU/kg of vitamin D3 for 8 weeks. The levels of CCL-5 (P<0.001) and CCR5 (P=0.003) were found to be higher in the DC group as compared to the HC group. However, when HIIT training and vitamin D3 were administered together, there was a decrease in CCL-5 (P=0.001) and CCR5 (P<0.001) in the DHIITD3 group (P=0.001). Similarly, vitamin D3 alone reduced CCR5 levels in the DD3 group (P< 0.001). Also, the decrease of CCR5 in the DD3 group was higher than in the DHIIT group (P=0.022), and the DHIITD3 group was higher than in the DHIIT group (P<0.001), but there was no difference between the DD3 and DHIITD3 groups (P≥0.05). The results indicate that combining HIIT training with vitamin D3 has a greater effect on reducing the expression of CCL-5 and CCR5 in the white adipose tissue of rats with type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), compared to the effects of each one alone. It is recommended that the study be conducted by measuring the variables involved in the mechanisms and the changes in CCL-5 and CCR5.

The effect of high-intensity interval, aerobic, resistance and spirulina supplement consumption on levels of UCP-1, TRPV1 and HOMA-IR in the white adipose tissue of diabetic rats

The purpose of this study was to investigate the effect of high-intensity interval, aerobic, and resistance training, and spirulina supplement consumption on the levels of Uncoupling Protein-1 (UCP1), Transient Receptor Potential Vanilloid (TRPV1) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in the white adipose tissue of diabetic rats. A total of 42 male rats with diabetes type II were randomly assigned into seven groups as follows: aerobic training (n=6), resistance training (n=6), interval training (n=6), aerobic training combined with supplementation (n=6), resistance training combined with supplementation (n=6), interval training combined with supplementation (n=6) and control (n=6) groups. The training groups carried out the training (8 weeks/5 days) on a rodent treadmill and ladder. The paired sample t-test and one-way ANOVA were employed for data analysis. The three kinds of training, with and without supplementation, significantly reduced mass, glucose, insulin, and insulin resistance. In the three supplementation-combined training groups the difference on the HOMA-IR index was significant; however, the decline was larger in the resistance training with supplementation group. The concentration of UCP-1 and TRPV1 proteins significantly increased in all training groups, with and without supplementation. Nonetheless, the significant increase in the UCP-1 levels in the interval training with supplementation group was more than in the other groups. Furthermore, the TRPV1 protein levels were higher in the resistance training with supplementation group. Eight weeks of training, with and without Spirulina supplementation, reduced insulin resistance and gave rise to significant changes in UCP-1 and TPRV1 concentrations.

The Effect of Swimming Training with Cinnamon Consumption on β3-AR and ERK2 Gene Expression in the Visceral Adipose Tissue of Diabetic Rats

Background: β3-AR is an important factor involved in the activation of ERK protein signaling cascade, which can positively contribute to the regulation of adipose tissue metabolism and its conversion into brown adipose tissue. Diabetes mellitus can lead to dysfunction of these factors. Objectives: The current study aimed to investigate the effect of swimming training combined with cinnamon consumption on β3-AR and ERK2 gene expression in the visceral adipose tissue from diabetic rats. Methods: In this experimental-fundamental study, 35 male Wistar rats (mean weight: 200 ± 20 g) were selected and randomly assigned into four groups after the induction of diabetes by streptozotocin. These groups included: (1) healthy control, (2) control, (3) swimming, (4) cinnamon, and (5) swimming cinnamon (n = 7 in each group). The training groups were put through a five-days-a-week workout for four weeks according to the training protocol. Gene expression levels were measured by in vitro real-time PCR. The collected data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: The expression levels of β3-AR and ERK2 protein genes in the visceral adipose tissue of diabetic rats (P = 0.0001) were significantly affected by swimming training and cinnamon consumption. Conclusions: It was shown that cinnamon supplementation may have increased β3-AR levels, which was more effective than training, while training had a greater effect on ERK2 levels and increased them. Therefore, it was concluded that cinnamon consumption combined with training may have greatly contributed to the conversion of white adipose into brown adipose tissues.

The effect of aerobic, resistance, and concurrent training on the expression and protein levels of RBP4 visceral and subcutaneous adipose tissue in diabetic rats with STZ

The effect of aerobic, resistance, and concurrent training on the expression and protein levels of RBP4 visceral and subcutaneous adipose tissue in diabetic rats with STZ

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing.

This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

The Effect of Swimming Training and Cinnamon Consumption on the Gene Expression of GLUT4 and Insulin Receptor in the Brown Adipose Tissue of Diabetic Rats

Background: The effect of training on the gene expression of GLUT4 and insulin receptor (IR) has been investigated in some studies, but the simultaneous effect of swimming training along with cinnamon consumption is unknown. Objective: This study aimed to examine the effect of six weeks of swimming training with cinnamon consumption on the gene expression of GLUT4 and IR in the brown adipose tissue of diabetic rats. Methods: In this experimental study, 28 diabetic rats were randomly divided into four groups of seven animals, including 1- control (C), 2- cinnamon (Ci), 3- swimming (S), and 4- swimming plus cinnamon (S + Ci). Rats in groups 3 and 4 trained for six weeks and five sessions. Groups 2 and 4 received 200 mg/kg/day. Data were analyzed using one-way analysis of variance and Tukey’s post hoc test at the level of P ≤ 0.05. Results: The gene expression of GLUT4 and IR in the S, Ci, and S + Ci groups was significantly (P = 0.001) higher than the control group. Also, the gene expression of GLUT4 and IR in the S group was significantly (P = 0.001) higher than the Ci and S + Ci groups. Conclusion: Swimming training and cinnamon consumption and their simultaneous implementation had a significant effect on increasing the gene expression of GLUT4 and IR in the brown adipose tissue of diabetic rats. On the other hand, swimming training alone had a greater effect than cinnamon consumption and swimming plus cinnamon consumption.

L-carnitine improves metabolic disorders and regulates apelin and apelin receptor genes expression in adipose tissue in diabetic rats.

Apelin is a new adipocytokine that acts as an endogenous hormone in various tissues through its receptor (APJ). This study aimed to investigate the effects of oral administration of L‐carnitine (LC) on the expression of Apelin and APJ in adipose tissue of experimentally induced insulin‐resistant and type 2 diabetic rats. In this experimental study, 60 male rats fed with high fat/high carbohydrate (HF/HC) diet. After 50 mg/kg intraperitoneally injection of streptozotocin (STZ) and confirmation of diabetes (FBS higher than 126 mg/dl), the animals were daily treated with 300 mg/kg LC for 28 days. At days 7, 14, and 28 of posttreatment, the expression of apelin and APJ in adipose tissue were determined using qPCR in diabetic, diabetic + LC treated, control, and control + LC treated groups. Apelin, insulin, TNF‐α, and IL1‐β were measured by the ELISA method. Results demonstrated that the rats fed with the HF/HC diet for 5 weeks were hyperinsulinemic and normoglycemic, while after STZ injection, they showed hyperinsulinemia and hyperglycemia with higher levels of HOMA‐IR. Apelin serum level, APJ and apelin gene expression in adipose tissue increased significantly with the development of diabetes compared to the control group. Treatment with LC for 14 days caused a reduction in apelin and APJ expressions in adipose tissue of diabetic rats. TNF‐α and IL1‐β levels were reduced in diabetic rats 14 days after their treatment with LC. The study results show that L‐carnitine could act as a new regulator in apelin gene expression in adipose tissue, improving the metabolic disorders in diabetic patients.

The localization of HPV and CMV in the adipose tissues of female diabetic type 1 rats and the possibility of having a role of reactivity of COVID-19 in diabetic subjects as a new medical hypothesis

Introduction: Diabetes has various impacts on human body. It is thought that diabetes is predisposed by obesity. Obesity may due to several factors including genetically-environmental factors. The recent views that viruses may act as etiology for obesity. Study objectives: The main objectives of the present study were to investigate the possibility that CMV and HPV of having a role in initiating episodes of obesity and diabetes, and to test the hypothesis that co-existence of multi-viruses including corona virus may work synergistically to increase the impact of COVID-19 on diabetic patients. Methodology: In this study, a diabetic model was induced, the localization of HPV and CMV was determined using immunohistochemistry. Results: Study findings showed that both viruses HPV and CMV exist in the adipose tissue of diabetic rats. Both viruses were brown in color. Conclusions: Taken together, both CMV and HPV exist in the adipose tissue of diabetic rats, and this may explain the phenomenon of autoimmunity in diabetes from one side and from another side, we may explain the occurrence of synergistic effects of COVID-19 virus and the other viruses mentioned in this study.

Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats.

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats.

It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic‐euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK‐2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin‐induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.

Effects of leptin on lipid metabolism and inflammatory factors in diabetic rats

Objective: To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 μg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Results: Compared with the control group, the blood glucose levels of other groups were increased significantly (P＜0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P＜0.05, P＜0.01). The insulin level of high dose leptin group decreased significantly (P＜0.01). There was no significant difference in FBG and INS among the three groups (P＞0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P＜0.05, P＜0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P＜0.05), HDL-C level of high dose group was increased significantly (P＜0.01). Compared with different dose groups, the high dose of leptin (100 μg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P＜0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. Conclusion: The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 μg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.

Protein-rich extract of Musca domestica larvae alleviated metabolic disorder in STZ-induced type 2 diabetic rat model via hepatoprotective and pancreatic β-cell protective activities

The study was designed to explore the beneficial effect of Musca domestica larvae extract (MDLE) on a metabolic disorder using a diabetic rat model. Streptozotocin-induced diabetic rats were treated with or without MDLE. Blood glucose, insulin levels, lipid profiles, and oxidative stress markers were measured. The morphological changes in the pancreas and liver were determined, as well as insulin expression. The expression of glucose transporter 4 (GLUT4), phospho-adenosine monophosphate-activated protein kinase (p-AMPK)/total AMPK, superoxide dismutase 1 (SOD1), catalase (CAT), and peroxisome proliferator-activated receptor gamma (PPARγ) were detected. Compared with untreated diabetic rats, MDLEtreated rats had decreased urine volume, food intake, and water intake, along with significantly lower levels of blood glucose, malondialdehyde (MDA), plasma triglycerides, low-density lipoprotein (LDL), and total cholesterol. MDLEtreated rats also had higher levels of SOD activity, high-density lipoprotein (HDL), and insulin. MDLE treatment partially restored the β-cell population, improved the liver necrosis and islet cell damage, reversed the decreased expression of GLUT4, phospho-AMPK, SOD1, and CAT in the liver, skeletal muscle and pancreatic tissue, and also increased the expression of PPARγ in the liver and adipose tissue in diabetic rats. In conclusion, the obtained results suggest that MDLE could possibly be used pharmacologically as an adjuvant for the treatment of diabetes.

Effect of resveratrol on resistin and apelin gene expressions in adipose tissue of diabetic rats.

Adipose tissue plays a major role in glucose homeostasis. Dietary antioxidants such as resveratrol (RSV) may offer some protection against the early stage of diabetes mellitus and the development of complications. The present study investigated the effects of RSV on biochemical parameters and resistin and apelin gene expressions in adipose tissue of rats with type 2 diabetes. Diabetes was induced using a single dose of streptozotocin + nicotinamide. Three groups of diabetic rats were treated with different doses of RSV (1, 5, and 10 mg/kg body weight per day). Oxidative status, serum biochemical parameters, insulin, and HOMA index were measured. Finally, resistin and apelin gene expressions were determined in rats' adipose tissue using RT- PCR (qRT-PCR). A significant reduction in serum glucose level was observed in rats treated with 5 and 10 mg/kg per day RSV compared with the diabetic control. Resistin expression in adipose tissue was reduced in RSV-treated groups, while no significant changes were observed in apelin expression. The results showed that RSV improves insulin sensitivity due to a simultaneous decrease in blood glucose and an increase in insulin. We concluded that RSV has potential hypoglycemic effect, probably by increasing insulin levels and changing the expression of resistin.

Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats

The effects of the proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)-β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed. Six-week-old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation. ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF-β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT. For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot-specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI-induced lipid synthesis in scWAT.

Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells

BackgroundVaspin is an adipocytokine that was recently identified in the visceral adipose tissue of diabetic rats and has anti-diabetic and anti-atherogenic effects. We hypothesized that vaspin prevents inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells.MethodsWe examined the effects of vaspin on NF-κB activation and the expression of the NF-κB-mediated genes intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Human aortic endothelial cells (HAECS) were used. Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine.ResultsTreatment with vaspin significantly increased the phosphorylation of AMPK and acetyl-CoA carboxylase, the down-stream target of AMPK. Furthermore, treatment with vaspin significantly decreased TNFα-induced activation of NF-κB, as well as the expression of the adhesion molecules ICAM-1, VCAM-1, E-selectin, and MCP-1. These effects were abolished following transfection of AMPKα1-specific small interfering RNA. In an adhesion assay using THP-1 cells, vaspin reduced TNFα-induced adhesion of monocytes to HAECS in an AMPK-dependent manner.ConclusionsVaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-κB following AMPK activation.

Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats.

Present study is an attempt to investigate plausible mechanism involved behind antidiabetic activity of standardized Houttuynia cordata Thunb. extract in streptozotocin-induced diabetic rats. The plant is used as a medicinal salad for lowering blood sugar level in North-Eastern parts of India. Oral administration of extract at 200 and 400 mg/kg dose level daily for 21 days showed a significant (P < 0.05) decrease in fasting plasma glucose and also elevated insulin level in streptozotocin-induced diabetic rats. It also significantly reversed all the alterations in biochemical parameters, that is, total lipid profile, blood urea, creatinine, protein, and antioxidant enzymes in liver, pancreas, and adipose tissue of diabetic rats. Furthermore, we have demonstrated that the extract significantly reversed the expression patterns of various glucose homeostatic enzyme genes like GLUT-2, GLUT-4, and caspase-3 levels but did not show any significant effect on PPAR-γ protein expressions. Additionally, the extract positively regulated mitochondrial membrane potential and succinate dehydrogenase (SDH) activity in diabetic rats. The findings justified the antidiabetic effect of H. cordata which is attributed to an upregulation of GLUT-4 and potential antioxidant activity, which may play beneficial role in resolving complication associated with diabetes.

Vaspin Increases Nitric Oxide Bioavailability through the Reduction of Asymmetric Dimethylarginine in Vascular Endothelial Cells

Vaspin is an adipocytokine recently identified in the visceral adipose tissue of diabetic rats and having anti-diabetic effects. We have recently shown that vaspin has anti-atherogenic effect through Akt-mediated inhibition of endothelial cell apoptosis. Decreased activity of endothelial nitric oxide synthase (eNOS) plays an important role in the pathogenesis of atherosclerosis. Asymmetric dimethylarginine (ADMA) is a well-known endogenous competitive inhibitor of eNOS and risk factor of cardiovascular diseases. The aim of this study was to examine whether vaspin might protect against atherosclerosis through its beneficial effects on the ADMA-eNOS system. Treatment of vaspin significantly increased NO secretion from endothelial cells and isolated aorta from Sprague-Dawley (SD) rats. Furthermore, treatment of vaspin prevented fatty acid-induced decrease in endothelium-dependent vasorelaxation in isolated aorta of SD rat. For the mechanism of vaspin-induced NO biosynthesis, vaspin activated the STAT3 signaling pathway and stimulated eNOS phosphorylation (Ser 1177), a marker of eNOS activation, through STAT3-dependent mechanism. Furthermore, vaspin treatment increased the expression of dimethylarginine dimethylaminohydrolase (DDAH) II, the responsible enzyme for the degradation of ADMA, leading to a reduction in ADMA levels. Vaspin-induced increase in DDAH II gene expression was through STAT3-mediated stimulation of DDAH II promoter activity. These results suggest that vaspin increases eNOS activity by reducing ADMA level through STAT3-mediated regulation of DDAH II expression. Our findings provide a novel molecular mechanism of antiatherogenic actions of vaspin.

Proinsulin C-Peptide Inhibits Lipolysis in Diabetic Rat Adipose Tissue Through Phosphodiestrase-3B Enzyme

We have previously reported that C-peptide modulates insulin-mediated inhibition of lipolysis and glucose consumption but has no significant effects per se on adipose tissue of normal rats. It has been repeatedly observed that certain actions of C-peptide are restricted to the diabetic states. In the present study, therefore, we examined whether C-peptide alters lipolysis in adipose tissue of diabetic rats. Rats were rendered diabetic by streptozotocin and divided into 2 groups; insulin treated and untreated. Retroperitoneal adipose tissue was excised aseptically, subjected to organ culture and incubated with rat C-peptide, insulin, or a combination of both peptides in the presence or absence of isoproterenol. Tissue lipolysis was assessed by the rate of glycerol release into the culture media. The cultures were pretreated with cilostamide, a phosphodiesterase-3B enzyme inhibitor, when the role of this enzyme was to be examined. C-Peptide on its own, like insulin, significantly inhibited isoproterenol-stimulated lipolysis in the adipose tissue of untreated diabetic rats. The effect was enhanced by a combination of C-peptide and insulin. Notably, the C-peptide's effect was totally blocked in the presence of cilostamide. In the adipose tissue of insulin treated rats, however, C-peptide failed to show any significant antilipolytic effects. These data show that C-peptide has the potential to act, conditionally, as an antilipolytic hormone by activating phosphodiesterase-3B and suggest that the action may contribute to the C-peptide's beneficial effects on diabetes-induced complications.

Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes

Berberine has hypoglycemic and hypolipidemic effects on diabetic rats. This study investigated the relationship between hypoglycemic and hypolipidemic effects of berberine and peroxisome proliferator-activated receptors (PPARs) and positive transcription elongation factor b (P-TEFb) (including cyclin-dependent kinase 9 (CDK9) and cyclin T1) in white adipose tissue of diabetic rats and RNA interference-treated 3T3-L1 cells. Berberine promoted differentiation and inhibited lipid accumulation of 3T3-L1 cells, further decreased PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression and decreased tumor necrosis factor α content in supernatants of both control and RNA interference-treated 3T3-L1 cells. After a 16-week induction with 35 mg/kg streptozotocin (i.p.) and high-carbohydrate/high-fat diet, diabetic rats were treated with 75, 150 and 300 mg/kg berberine and 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone for another 16 weeks. Berberine decreased white adipose tissue to body weight ratio and adipocyte size and increased adipocyte number. Berberine upregulated PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression in adipose tissue, decreased tumor necrosis factor α and free fatty acid content and increased lipoprotein lipase activity in serum and adipose tissue. Berberine modulated metabolic related PPARs expression and differentiation related P-TEFb expression in adipocytes, which are associated with its hypoglycemic and hypolipidemic effects.

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 +/- 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 +/- 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 +/- 1.28 x 10(-8) micromol/mg/min) was significantly higher than that in the diabetic rats (1.26 +/- 0.35 x 10(-8); p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.