Invited Review : Altitude training as a powerful corrective intervention in correctin insulin resistance

( Shu Man Chen ),( Chia Hua Kuo ) 한국운동영양학회 2012 Physical Activity and Nutrition (Phys Act Nutr) Vol.16 No.2

Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3, 4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/−Mice Mediated by miR-33

Chen-Yi Tang,Xiao-Fei Man,Yue Guo,Hao-Neng Tang,Jun Tang,Ci-La Zhou,Shu-Wen Tan,Min Wang,Hou-De Zhou 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1−/−) with growth retardation and subcutaneous adipocyte atrophy. Irs-1−/− mice exhibited mild insulin resistance, as demonstrat-ed by the insulin tolerance test. Phosphatidylino-sitol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcu-taneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1−/− mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1−/− mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1^-/- Mice Mediated by miR-33

Tang, Chen-Yi,Man, Xiao-Fei,Guo, Yue,Tang, Hao-Neng,Tang, Jun,Zhou, Ci-La,Tan, Shu-Wen,Wang, Min,Zhou, Hou-De Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

WEIGHTED EVIDENTIAL FUSION METHOD FOR FAULT DIAGNOSIS OF MECHANICAL TRANSMISSION BASED ON OIL ANALYSIS DATA

Yan Shu-fa,Ma Biao,Zheng Chang-song,Chen Man 한국자동차공학회 2019 International journal of automotive technology Vol.20 No.5

Condition monitoring (CM) and fault diagnosis are critical for the stable and reliable operation of mechanical transmissions. Mechanical transmission wear, which leads to changes in the physicochemical properties of the lubrication oil and thus severe wear, is a slow degradation process that can be monitored by oil analysis, but the actual degradation degree is difficult to evaluate. To solve this problem, we propose a new weighted evidential data fusion method to better characterize the degradation degree of the mechanical transmission through the fusion of multiple CM datasets from oil analysis. This method includes weight allocation and data fusion steps that lead to a more accurate data-based fault diagnostic result for CM. First, the weight of each evidence is modeled with a weighted average function by measuring the relative scale of the permutation entropy from each CM dataset. Then, the multiple CM datasets are fused by the Dempster combination rule. Compared with other evidential data fusion methods, the proposed method using the new weight allocation function seems more reasonable. The rationality and superiority of the proposed method were evaluated through a case study involving an oilbased CM dataset from a power-shift steering transmission.

The influence of the extent of lymph node metastasis on the prognosis for patients with intrahepatic cholangiocarcinoma

Jianping Wang*,Man Shu*,Hong Peng,Shaoqiang Li,Dongming Li,Jingxian Shen,Ming Kuang,Ying Zhang,Zebin Chen 대한외과학회 2023 Annals of Surgical Treatment and Research(ASRT) Vol.104 No.5

Purpose: Reports showed that some of intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM) may also gain survival benefit undergone resection. However, the effect of the extent of LNM on prognosis and surgical indication is barely discussed. Methods: From September 1994 to November 2018, primary ICC patients undergone initial curable surgery were enrolled. Based on the extent of LNM, we divided these patients into 4 groups, including patients with no LNM (group N0), LNM to hepatoduodenal ligament or common hepatic artery (region A, group A), LNM to gastrohepatic lymph nodes for left liver ICC and periduodenal and peripancreatic lymph node for right liver ICC (region B, group B), or LNM beyond these regions (region C, group C). Multivariable Cox regression analysis was performed to identify the prognostic factors for recurrence- free survival (RFS) and overall survival (OS) in all groups. Results: A total of 133 patients were enrolled. There were 56, 21, 17, and 39 patients in groups N0, A, B, and C, respectively. There was significant difference between groups N0 and C in RFS (P < 0.001) and OS (P = 0.002). When we compared group N0 + A + B with group C, we also found that RFS (P < 0.001) and OS (P = 0.007) were significantly different. In multivariable analysis, the extent of LNM was an independent risk factor for RFS (P < 0.050). Conclusion: ICC patients with the LNM to regions A and B could still achieve good prognosis with resection. Surgery should be carefully considered when LNM to region C.

Decreased Expression of FADS1 Predicts a Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Du, Yong,Yan, Shu-Mei,Gu, Wan-Yi,He, Fan,Huang, Li-Yun,Li, Mei,Yuan, Yan,Chen, Ren-Hui,Zhong, Qian,Li, Man-Zhi,Li, Yong,Zeng, Mu-Sheng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.

The Prognostic Value of CD8+ and CD45RO+ T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation

Hong Jiang,Pengfei Gao,Huadong Chen,Zhihai Zhong,Man Shu,Zhichong Zhang,Jinbiao She,Juncheng Liu 대한의학회 2018 Journal of Korean medical science Vol.33 No.30

Background: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors Methods: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+ , CD8+ , CD45RO+ , CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. Results: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022–0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37–11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018–0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. Conclusion: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.

cDNA cloning, expression, and immunolocalization of gonadinhibiting hormone (GIH) in Litopenaeus vannamei

Guang-li Li,Si-ping Deng,Shu-na Jiang,Man Ye,Hua-pu Chen,Siuming F. Chan,Chun-hua Zhu 한국유전학회 2015 Genes & Genomics Vol.37 No.10

In this study, the full-length GIH cDNA sequence from Litopenaeus vannamei was cloned from the eyestalk by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. The fulllength GIH cDNA was 865 bp with a 288 bp open-reading frame, which encoded a 96 amino acid prepro-GIH with 17 amino acid signal peptide. L. vannamei GIH (LvGIH) can be classified as a member of type-II crustacean hyperglycemic hormone polypeptide family. LvGIH shares 93.8 and 66.7 % amino acid sequence identity with GIH from Penaeus monodon, and the molt-inhibiting hormone from Marsupenaeus japonicas, respectively. By quantitative real-time PCR (qPCR), LvGIH mRNA transcripts were detected in fertilized eggs, nauplius, zoea, mysis and juveniles of 25, 35 and 40 days old. LvGIH transcript levels increased significantly with the development from fertilized eggs to juveniles. LvGIH transcript levels were highest in juveniles at 35 days old. By RT-PCR, LvGIH mRNA transcripts were detected only in the eyestalks and brains but not in the muscles, intestines, gills, heart, hepatopancreas, ovaries and testes of adults, and there was no difference in the expression level of LvGIH between males and females. Using the P. monodon anti-GIH antibody, we showed that LvGIH was located mainly in the XO-SG and slightly in axon, with similar fluorescence intensity found in XO and SG. To summarize, we have cloned and characterized the GIH of the shrimp L. vannamei. In addition to the GIH properties described in other crustaceans, a peak of LvGIH expression was identified at the time of sexual differentiation (i.e., day 35 larvae) suggesting that LvGIH may also be involved in the control of this process.