Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcu...Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-Insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.展开更多
Objective： To investigate the effect of Xuezhikang（血脂康, XZK） on renal cell apoptosis in diabetic rats and the possible mechanism. Methods： Sixty-six rats were randomly divided into 3 groups： the normal, model ...Objective： To investigate the effect of Xuezhikang（血脂康, XZK） on renal cell apoptosis in diabetic rats and the possible mechanism. Methods： Sixty-six rats were randomly divided into 3 groups： the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK（1200 mg/kg body weight） everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours＇ urine was collected for urinary albumin excretion（UAE） measurement. Periodic acid-Schiff（PAS） and Masson＇s trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling（TUNEL） staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C（Cyt C） and caspase-9 concentration were detected by Western blot. Results： Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months（P〈0.05 or P〈0.01）. Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson＇s trichromestained collagen to different extent. Conclusions： Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.展开更多
Objective Houttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine（TCM） compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical t...Objective Houttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine（TCM） compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical therapy for diabetic nephropathy. On the basis of the TCM theory of heat in diabetes mellitus and the clinical efficacy of Fructus Arctii, the two compounds were used to develop a formula named Compound Herba Houttuyniae. This study evaluated the renoprotective effects of different Compound Herba Houttuyniae extracts and assessed their mechanisms through the Janus kinase/signal transducer and activator of transcription（JAK/STAT）–suppressors of cytokine signaling（SOCS）-1 pathway. Methods The normal group comprised db/m mice（n = 8）; db/db mice were randomly divided into six groups according to the applied treatment method： model group（no treatment）, AG490 group, petroleum ether extract（PEE） group, ethyl acetate extract（EAE） group, N-butanol extract（NE） group, and water extract（WE） group（n = 6 in each group）. The general status, biochemical indicators, and renal histological changes in the mice were evaluated, and the JAK/STAT–SOCS-1 pathway was assessed. Results The NE and WE groups showed a decrease in 24-h urinary protein and albumin levels as well as serum uric acid and fibronectin levels but showed no changes in fasting plasma glucose and hemoglobin A1 c levels. The protein expression of JAK2, STAT3, P-JAK2, and P-STAT3 and the gene expression of JAK2 and STAT3 in kidney tissues were significantly increased（P 〈 0.05） in the model group. Compared with the model group, the expression of P-JAK2 and P-STAT3 was downregulated in the extract treatment groups. The expression of SOCS-1 was increased in the NE and WE groups（P 〈 0.05）. However, the expression of JAK2, STAT3, JAK2 m RNA, and STAT3 m RNA in the treatment groups did not show any significant differences. Conclusion Compound Herba Houttuyniae showed renoprotective effects in db/db mice, and the strongest effects were observed in the WE and NE groups. The underlying mechanism for these effects might involve the regulation of the JAK/STAT–SOCS-1 pathway.展开更多
文摘Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-Insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.
文摘Objective： To investigate the effect of Xuezhikang（血脂康, XZK） on renal cell apoptosis in diabetic rats and the possible mechanism. Methods： Sixty-six rats were randomly divided into 3 groups： the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK（1200 mg/kg body weight） everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours＇ urine was collected for urinary albumin excretion（UAE） measurement. Periodic acid-Schiff（PAS） and Masson＇s trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by Td T-mediated d UTP nick end labeling（TUNEL） staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C（Cyt C） and caspase-9 concentration were detected by Western blot. Results： Compared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months（P〈0.05 or P〈0.01）. Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson＇s trichromestained collagen to different extent. Conclusions： Renal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.
基金National Natural Science Foundation of China(No.81403345)Innovation Program of Shanghai Municipal Education Commission(No.14YZ059)
文摘Objective Houttuynia cordata Thunb and Fructus Arctii are two traditional Chinese medicine（TCM） compounds widely used for reducing heat and toxins in the body. In addition, Fructus Arctii has been used in clinical therapy for diabetic nephropathy. On the basis of the TCM theory of heat in diabetes mellitus and the clinical efficacy of Fructus Arctii, the two compounds were used to develop a formula named Compound Herba Houttuyniae. This study evaluated the renoprotective effects of different Compound Herba Houttuyniae extracts and assessed their mechanisms through the Janus kinase/signal transducer and activator of transcription（JAK/STAT）–suppressors of cytokine signaling（SOCS）-1 pathway. Methods The normal group comprised db/m mice（n = 8）; db/db mice were randomly divided into six groups according to the applied treatment method： model group（no treatment）, AG490 group, petroleum ether extract（PEE） group, ethyl acetate extract（EAE） group, N-butanol extract（NE） group, and water extract（WE） group（n = 6 in each group）. The general status, biochemical indicators, and renal histological changes in the mice were evaluated, and the JAK/STAT–SOCS-1 pathway was assessed. Results The NE and WE groups showed a decrease in 24-h urinary protein and albumin levels as well as serum uric acid and fibronectin levels but showed no changes in fasting plasma glucose and hemoglobin A1 c levels. The protein expression of JAK2, STAT3, P-JAK2, and P-STAT3 and the gene expression of JAK2 and STAT3 in kidney tissues were significantly increased（P 〈 0.05） in the model group. Compared with the model group, the expression of P-JAK2 and P-STAT3 was downregulated in the extract treatment groups. The expression of SOCS-1 was increased in the NE and WE groups（P 〈 0.05）. However, the expression of JAK2, STAT3, JAK2 m RNA, and STAT3 m RNA in the treatment groups did not show any significant differences. Conclusion Compound Herba Houttuyniae showed renoprotective effects in db/db mice, and the strongest effects were observed in the WE and NE groups. The underlying mechanism for these effects might involve the regulation of the JAK/STAT–SOCS-1 pathway.
