In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify ...In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.展开更多
Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, ...Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells （HUVECs） induced by an intermittent high-glucose media and its association with adiponectin receptor 1 （adipoR1）, adipoR2, or adenosine monophosphate （AMP）-activated protein kinase （AMPK）. Methods HUVECs were cultured in continuous normal glucose （5.5 mmol/L）, continuous high glucose （25 mmol/L）, alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA （siRNA） and then stimulated with globular adiponectin （gAD）. Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside （AICAR）. Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside （araA）, gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.展开更多
AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on...AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is reduced in fat- fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar fi ndings have been described in humans. Diminished hepatic expression of adiponectinreceptors was only found in liver cirrhosis.展开更多
Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic eff...Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.展开更多
AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal ...AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P < 0.05). The effects of ADPN were no longer observed in the presence of the nitric oxide(NO) synthesis inhibitor L-NG-nitro arginine(L-NNA)(P > 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.展开更多
Pancreatic ductal adenocarcinoma(PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive gene...Pancreatic ductal adenocarcinoma(PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks(sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ(PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stressassociated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.展开更多
AIM:To explore the therapeutic role of globular adiponectin(gAd)in high-fat diet/streptozotocin(STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease(NAFLD).METHODS:Seven rats were fed a basic diet(n...AIM:To explore the therapeutic role of globular adiponectin(gAd)in high-fat diet/streptozotocin(STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease(NAFLD).METHODS:Seven rats were fed a basic diet(normal control group;NC)during the experiment.Experimental rats(14 rats)were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus(T2DM)and NAFLD.Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d(gAd-treated group),while the other 7 rats(T2DM/NAFLD group)received 0.9%saline.Plasma biochemical parameters and insulin concentrations were measured.Liver histopathology was examinedby hematoxylin-eosin staining.Insulin receptor expression in the liver was analyzed by immunohistochemical staining,Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis.RESULTS:Compared to the control group,the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin.Plasma glucose and lipid levels were decreased in the gAd-treated group,while serum insulin levels increased.The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group,and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats.Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group(NAS 1.39±0.51 vs 1.92±0.51,P<0.05).CONCLUSION:Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion,mediating glucolipid metabolism,regulating insulin receptor expression and alleviating hepatic steatosis.展开更多
Background: While the various antitumororal activities of adiponectin as an adipocyte-derived hormone well studied, it is speculated that there is a crosstalk between adiponectin and esterogen receptor (ER) signaling....Background: While the various antitumororal activities of adiponectin as an adipocyte-derived hormone well studied, it is speculated that there is a crosstalk between adiponectin and esterogen receptor (ER) signaling. To test this hypothesis we evaluate the possible correlation between serum level of adiponectin with two estrogen receptors (ERα and ERβ) gene expression in breast cancer patients. Methods: In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI 2 and 34 obese, BMI ≥ 25 kg/m2).The mean age of Participants was 44.53 yr ± 1.79 yr (21 yr - 70 yr) .Serum level of adiponectin determined by ELISA. Following quantitative expression of estrogen receptors mRNA in tumor tissues was evaluated by Real-time PCR. Results: We find a significant reverse correlation between serum level of Adiponectin and ERα mRNA (r = –0.229, n = 64, p = 0.035) but no correlation was between adiponectin and ERβ in samples (p = 0.228). The lower adiponectin multiplied the odds of having higher ERα mRNA level by a factor of OR = 4.33, 1.28 - 14.6, 95% confidence interval (CI) as compared with those that displayed a moderate or higher serum level of adiponectin (>7.02 ng/ml). The same odds for next estrogen receptor, ERβ, was not greater than unity (OR = 0.31, 0.06 - 1.56, 95% CI). Conclusion: According to the obtained results, it is speculated that as adiponectin can affect ERs gene expression, so affecting the steroid receptor signaling can be proposed as a new underling mechanism of action for this adipokine in breast cancer pathogenesis especially in obese ones.展开更多
文摘In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.
基金Acknowledgments This study was funded by the National Natural Science Foundation of China （81570323, 30972709, 81061120527, 81241082） and the 12th Five-Year National Program of the Ministry of Scientific Technology （2012BAI10B01）. We thank Liu M and Zhou L from Beijing Hospital for providing experimental data, the nurses from Beijing Anzhen Hospital for collecting specimens, and the study volunteers.
文摘编码 adiponectin 受体 1 的基因( ADIPOR1 )和小象ubiquitin一样修饰词( SUMO4 ) 4 被连接了到 anti-atherogenic 效果，但是很少对是否被知道在二基因的多型性，独立行动或交往，没有 diabetes.MethodsWe genotyped ，影响冠的动脉疾病( CAD )的风险没有糖尿病的 200 个 CAD 病人和没有 CAD 的 200 控制，它被选择基于前一个没有 diabetes.ResultsRisk 等位基因，协会也是的潜力在 ADIPOR1 (rs7539542-G， rs7514221-C 和 rs3737884-G ) 在三 SNP 在这些 SNP 和 CAD 的临床的特征之间探索了，没有糖尿病，在在 SUMO4 的 SNP rs237025 的 G 等位基因显著地增加了 CAD 的风险，与从 1.79 ～ 4.44 的 ORs。任何这四风险等位基因的搬运人出现了类似不利 ? 临床的特征。与有 CC 或 GC 遗传型的个人相比，有在 rs3737884 的 GG 遗传型的那些在影响了左前面的下降冠的动脉的 CAD 的显著地更高的风险(或：6.77， P = 0.009 ) ，恰好冠的动脉(或：4.81， P = 0.028 ) 或容器的一个相对大的数字(P = 0.04 ) 。没有糖尿病，在 SUMO4 在 SNP 象风险等位基因一样在 ADIPOR1 在三 SNP 中的至少一个带风险等位基因的个人比不带任何风险等位基因的个人在 CAD 的显著地更高的风险(或：5.82， 95% CI：1.2327.7， P = 0.013 ) 没有糖尿病，在 ADIPOR1 和 SUMO4 的 .ConclusionsSNPs 与 CAD 的提高的风险被联系，并且在二基因的 SNP 可以交往联合影响疾病风险。
文摘Background Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells （HUVECs） induced by an intermittent high-glucose media and its association with adiponectin receptor 1 （adipoR1）, adipoR2, or adenosine monophosphate （AMP）-activated protein kinase （AMPK）. Methods HUVECs were cultured in continuous normal glucose （5.5 mmol/L）, continuous high glucose （25 mmol/L）, alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoRl-specific small-interfering RNA （siRNA） and then stimulated with globular adiponectin （gAD）. Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-l-13-D-ribofuranoside （AICAR）. Third, cells were cultured in the AMPK inhibitor adenine-9-13-D-arabino-furanoside （araA）, gAD, and in AICAR. Results HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 pg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated. Conclusions We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose- evoked apoptosis in endothelial cells, gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.
基金Supported by a grant from the Deutsche Forschungsgemeinschaft (BU 1141/3-2)
文摘AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is reduced in fat- fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar fi ndings have been described in humans. Diminished hepatic expression of adiponectinreceptors was only found in liver cirrhosis.
基金Acknowledgment This research was supported by grants from the American Diabetes Association （1-11-JF56） and the Natural Science Foundation of China （30900592, 81170199） （to YJW） , and NIH （ HL-63828, HL-096686 ） and American Diabetes Association （7-11-BS-93） （to XLM）.
基金supported by Hong Kong Health and Medical Research FundLeading Talents of Guangdong(2013)+3 种基金Programme of Introducing Talents of Discipline to Universities(B14036)Project of International,as well as Hong Kong,Macao&Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province,China(2013gjhz0002)grants to Jinan University Guangdong-Hong Kong-Macao Cooperation and Innovation Center for Tissue Regeneration and RepairState Key Laboratory of Pharmaceutical Biotechnology,Hong Kong SAR,China
文摘Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.
基金the Florence University(No.RTD CO 090101010107 RICATEN14)Fondazione CRF(No.2017.0777)
文摘AIM To investigate whether the adipocytes derived hormone adiponectin(ADPN) affects the mechanical responses in strips from the mouse gastric fundus. METHODS For functional experiments, gastric strips from the fundal region were cut in the direction of the longitudinal muscle layer and placed in organ baths containing KrebsHenseleit solution. Mechanical responses were recorded via force-displacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparation was threaded. The effects of ADPN were investigated on the neurally-induced contractile and relaxant responses elicited by EFS. The expression of ADPN receptors, Adipo-R1 and Adipo-R2, was also evaluated by touchdown-PCR analysis. RESULTS In the functional experiments, EFS(4-16 Hz) elicited tetrodotoxin(TTX)-sensitive contractile responses. Addition of ADPN to the bath medium caused a reduction in amplitude of the neurally-induced contractile responses(P < 0.05). The effects of ADPN were no longer observed in the presence of the nitric oxide(NO) synthesis inhibitor L-NG-nitro arginine(L-NNA)(P > 0.05). The direct smooth muscle response to methacholine was not influenced by ADPN(P > 0.05). In carbachol precontracted strips and in the presence of guanethidine, EFS induced relaxant responses. Addition of ADPN to the bath medium, other than causing a slight and progressive decay of the basal tension, increased the amplitude of the neurally-induced relaxant responses(P < 0.05). Touchdown-PCR analysis revealed the expression of both Adipo-R1 and Adipo-R2 in the gastric fundus.CONCLUSION The results indicate for the first time that ADPN is able to influence the mechanical responses in strips from the mouse gastric fundus.
基金Supported by Fondo per gli Investimenti della Ricerca di BaseNo.RBAP10MY35_002+1 种基金Ente Cassa di Risparmio di Firenzeand Fior Gen ONLUS to Galli A
文摘Pancreatic ductal adenocarcinoma(PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks(sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ(PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stressassociated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.
基金Supported by Science and Technology Project of Xiamen,China,No.3502Z20114016
文摘AIM:To explore the therapeutic role of globular adiponectin(gAd)in high-fat diet/streptozotocin(STZ)-induced type 2 diabetic rats with nonalcoholic fatty liver disease(NAFLD).METHODS:Seven rats were fed a basic diet(normal control group;NC)during the experiment.Experimental rats(14 rats)were given a high-fat diet for 4 wk and were then injected with STZ to induce type 2 diabetes mellitus(T2DM)and NAFLD.Half of the T2DM/NAFLD rats were randomly injected intraperitoneally with gAd for 7 d(gAd-treated group),while the other 7 rats(T2DM/NAFLD group)received 0.9%saline.Plasma biochemical parameters and insulin concentrations were measured.Liver histopathology was examinedby hematoxylin-eosin staining.Insulin receptor expression in the liver was analyzed by immunohistochemical staining,Western blot and quantitative real-time reverse transcription polymerase chain reaction analysis.RESULTS:Compared to the control group,the T2DM/NAFLD group had increased levels of glucolipid and decreased levels of insulin.Plasma glucose and lipid levels were decreased in the gAd-treated group,while serum insulin levels increased.The expression of insulin receptor in the T2DM/NAFLD group increased compared with the NC group,and gAd downregulated insulin receptor expression in the livers of T2DM/NAFLD rats.Steatosis of the liver was alleviated in the gAd-treated group compared to the T2DM/NAFLD group(NAS 1.39±0.51 vs 1.92±0.51,P<0.05).CONCLUSION:Globular adiponectin exerts beneficial effects in T2DM rats with NAFLD by promoting insulin secretion,mediating glucolipid metabolism,regulating insulin receptor expression and alleviating hepatic steatosis.
文摘Background: While the various antitumororal activities of adiponectin as an adipocyte-derived hormone well studied, it is speculated that there is a crosstalk between adiponectin and esterogen receptor (ER) signaling. To test this hypothesis we evaluate the possible correlation between serum level of adiponectin with two estrogen receptors (ERα and ERβ) gene expression in breast cancer patients. Methods: In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI 2 and 34 obese, BMI ≥ 25 kg/m2).The mean age of Participants was 44.53 yr ± 1.79 yr (21 yr - 70 yr) .Serum level of adiponectin determined by ELISA. Following quantitative expression of estrogen receptors mRNA in tumor tissues was evaluated by Real-time PCR. Results: We find a significant reverse correlation between serum level of Adiponectin and ERα mRNA (r = –0.229, n = 64, p = 0.035) but no correlation was between adiponectin and ERβ in samples (p = 0.228). The lower adiponectin multiplied the odds of having higher ERα mRNA level by a factor of OR = 4.33, 1.28 - 14.6, 95% confidence interval (CI) as compared with those that displayed a moderate or higher serum level of adiponectin (>7.02 ng/ml). The same odds for next estrogen receptor, ERβ, was not greater than unity (OR = 0.31, 0.06 - 1.56, 95% CI). Conclusion: According to the obtained results, it is speculated that as adiponectin can affect ERs gene expression, so affecting the steroid receptor signaling can be proposed as a new underling mechanism of action for this adipokine in breast cancer pathogenesis especially in obese ones.
