Mar 2013, Volume 7 Issue 1
    

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  • EDITORIAL
    Weiping Jia
  • REVIEW
    Jingyi Lu, Guoxiang Xie, Weiping Jia, Wei Jia

    The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society. Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades, little progress has been made toward curing the disease or even getting it under control, from a public health and overall societal standpoint. There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses, highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications. The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites, which are sensitive to the changes of both environmental and genetic factors and therefore, could be regarded as the link between genotypes and phenotypes. During the last decade, the progression made in metabolomics has provided insightful information on disease development and disease onset prediction. Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered, including branched-chain and aromatic amino acids, such as isoleucine, leucine, valine, tyrosine and phenylalanine, as diagnostic or highly-significant predictors of future diabetes. This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes, type 2 diabetes.

  • REVIEW
    Jianping Ye

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

  • REVIEW
    Huating Li, Jing Zhang, Weiping Jia

    Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

  • REVIEW
    Xiao Miao, Weixia Sun, Yaowen Fu, Lining Miao, Lu Cai

    Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

  • REVIEW
    Jingyi Lu, Guoxiang Xie, Weiping Jia, Wei Jia

    Insulin resistance (IR) is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders. IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network. Branched-chain amino acids (BCAAs), namely valine, leucine and isoleucine, are among the nine essential amino acids, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency. Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight, it is only recently that BCAAs are found to be closely associated with IR. This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

  • REVIEW
    Zeng Zhang, Changqing Zhang, Zhenlin Zhang

    Digital clubbing, which has been recognized as a sign of systemic disease, is one of the most ancient diseases. However, the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood. The study of a clinically indistinguishable idiopathic form (primary hypertrophic osteoarthropathy, PHO) provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy. Current advances in the study of PHO are discussed. The impaired metabolism of prostaglandin E2 (PGE2) plays a central role in its pathogenesis.

  • REVIEW
    Eryuan Liao

    Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

  • REVIEW
    Wenbo Yan, Xin Li

    Diabetes mellitus is an enormous menace to public health globally. This chronic disease of metabolism will adversely affect the skeleton if not controlled. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are associated with an increased risk of osteoporosis and fragility fractures. Bone mineral density is reduced in T1DM, whereas patients with T2DM have normal or slightly higher bone density, suggesting impaired bone quality is involved. Detrimental effects of T1DM on the skeleton are more severe than T2DM, probably because of the lack of osteo-anabolic effects of insulin and other pancreatic hormones. In both T1DM and T2DM, low bone quality could be caused by various means, including but not limited to hyperglycemia, accumulation of advanced glycosylation end products (AGEs), decreased serum levels of osteocalcin and parathyroid hormone. Risk for osteoarthritis is also elevated in diabetic population. How diabetes accelerates the deterioration of cartilage remains largely unknown. Hyperglycemia and glucose derived AGEs could contribute to the development of osteoarthritis. Moreover, it is recognized that oral antidiabetic medicines affect bone metabolism and turnover as well. Insulin is shown to have anabolic effects on bone and hyperinsulinemia may help to explain the slightly higher bone density in patients with T2DM. Thiazolidinediones can promote bone loss and osteoporotic fractures by suppressing osteoblastogenesis and enhancing osteoclastogenesis. Metformin favors bone formation by stimulating osteoblast differentiation and protecting them against diabetic conditions such as hyperglycemia. Better knowledge of how diabetic conditions and its treatments influence skeletal tissues is in great need in view of the growing and aging population of patients with diabetes mellitus.

  • RESEARCH ARTICLE
    Renling Pei, Ye Xu, Yan Wei, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie

    It has been demonstrated that single nucleotide polymorphisms (SNPs) of SIPA1 (signal-induced proliferation associated gene 1) are associated with metastatic efficiency in both human and rodents. The purpose of this study was to determine whether SIPA1 545 C>T polymorphism was associated with overall survival in patients with metastatic breast cancer. In this study, SIPA1 545 C>T polymorphism was detected in 185 metastatic breast cancer patients using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Survival curves for patients with SIPA1 545 C>T polymorphism was compared using the Kaplan-Meier method with log-rank tests. We found that SIPA1 545 C>T polymorphism was significantly associated with survival in 185 patients with metastatic breast cancer. Patients with SIPA1 545 T/T genotype had a significantly worse overall survival (OS) than did patients with C/T or C/C genotype (50.0% vs. 62.9%, P = 0.042). Moreover, in multivariate analysis, as compared with the C/C or C/T genotype, the T/T genotype remained an independent unfavorable prognostic marker of OS in this cohort (hazard ratio [HR] = 2.16; 95% CI= 1.12–4.15; P = 0.022). Our findings indicate that metastatic breast cancer patients with SIPA1 545 T/T genotype have a poorer survival compared to patients with C/C or C/T genotype.

  • CASE REPORT
    Xiaoyan Chen, Xiaochun Huang, Yuan Qiu, Hanzhang Chen, Yingyu Fu, Xinchun Li

    Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.