Current drug targets. Immune, endocrine and metabolic disorders最新文献

筛选
英文 中文
Evidence for a putative relationship between type 2 diabetes and neoplasia with particular reference to breast cancer: role of hormones, growth factors and specific receptors. 2型糖尿病与肿瘤之间关系的证据,尤其是乳腺癌:激素、生长因子和特定受体的作用。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-03-01 DOI: 10.2174/1568008043339965
E Guastamacchia, F Resta, V Triggiani, A Liso, B Licchelli, S Ghiyasaldin, C Sabbà, E Tafaro
{"title":"Evidence for a putative relationship between type 2 diabetes and neoplasia with particular reference to breast cancer: role of hormones, growth factors and specific receptors.","authors":"E Guastamacchia,&nbsp;F Resta,&nbsp;V Triggiani,&nbsp;A Liso,&nbsp;B Licchelli,&nbsp;S Ghiyasaldin,&nbsp;C Sabbà,&nbsp;E Tafaro","doi":"10.2174/1568008043339965","DOIUrl":"https://doi.org/10.2174/1568008043339965","url":null,"abstract":"<p><p>The issue of a possible relationship between type 2 diabetes and cancer is still debated. Such chronic diseases show a high incidence in the general population. In their pathophysiology both genetic and environmental factors are involved, inducing important modifications of metabolism. Diabetes is associated to profound metabolic alterations, such as hyperinsulinemia and insulin resistance, which are common in various diseases, i.e. obesity, hypertension, dyslipidemia and hyperuricemia. Those illnesses form the so-called metabolic syndrome. Insulin resistance, hyperestrinism and the associated hyperandrogenism may play a role in the onset of some malignancies, such as endometrium cancer, breast cancer and prostate cancer. Low plasma levels of IGF-1 are able to reduce the risk of cancer in type 2 diabetes patients. This goal can be obtained with preventive measures, as physical activity, diet and drugs that can reduce insulin resistance (metformin and thiazolidinediones).</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 1","pages":"59-66"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 27
Participation of maternal and fetal CRH in early phases of human implantation: the role of antalarmin. 母体和胎儿CRH在人类着床早期的参与:安塔拉素的作用。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-03-01 DOI: 10.2174/1568008043339992
A Makrigiannakis, E Zoumakis, S Kalantaridou, G Chrousos, A Gravanis
{"title":"Participation of maternal and fetal CRH in early phases of human implantation: the role of antalarmin.","authors":"A Makrigiannakis,&nbsp;E Zoumakis,&nbsp;S Kalantaridou,&nbsp;G Chrousos,&nbsp;A Gravanis","doi":"10.2174/1568008043339992","DOIUrl":"https://doi.org/10.2174/1568008043339992","url":null,"abstract":"<p><p>The hypothalamic neuropeptide corticotropin-releasing hormone (CRH) is produced by several tissues of the female reproductive system. It is also secreted at inflammatory sites and possesses potent pro-inflammatory properties influencing both innate and acquired immune processes. Uterine CRH participates in local immune early pregnancy phenomena, such as decidualization of endometrial strom a and protection of the fetus from maternal immune system. This is maintained through induction of the expression of apoptotic FasL on invasive extravillous trophoblast and maternal decidual cells at the fetal-maternal interface. Furthermore, CRH increases apoptosis of activated T lymphocytes through FasL induction participating in the process of implantation and early pregnancy. Female rats treated with the non-peptidic CRH receptor 1 (CRHR1) specific antagonist antalarmin, in the first 6 days of gestation, have undergone a decrease of endometrial implantation sites and live embryos and markedly diminished endometrial FasL expression.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 1","pages":"75-8"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
The HIV-1 Nef protein: how an AIDS pathogenetic factor turns to a tool for combating AIDS. HIV-1 Nef蛋白:艾滋病致病因子如何转变为对抗艾滋病的工具。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-03-01 DOI: 10.2174/1568008043339983
I Schiavoni, C Muratori, V Piacentini, A M Giammarioli, M Federico
{"title":"The HIV-1 Nef protein: how an AIDS pathogenetic factor turns to a tool for combating AIDS.","authors":"I Schiavoni,&nbsp;C Muratori,&nbsp;V Piacentini,&nbsp;A M Giammarioli,&nbsp;M Federico","doi":"10.2174/1568008043339983","DOIUrl":"https://doi.org/10.2174/1568008043339983","url":null,"abstract":"<p><p>Nef is one of the six regulatory proteins coded by the Human Immunodeficiency Virus (HIV)-1 and -2, and by the Simian Immunodeficiency Virus (SIV). Accumulating experimental evidences indicate that Nef is required for the optimal infectivity of HIV viral particles, and that it plays a critical role in the AIDS pathogenesis progressing. We previously cloned and sequenced a functionally defective HIV-1 genome (F12HIV-1) whose nef gene showed a rather unusual feature, i.e. its expression blocks the HIV-1 release by interfering with the viral assembling/release. Such a striking phenotype appeared to be the result of three amino acid substitutions, and coupled with the loss of the most part of the Nef functions described for the wild type counterpart. The F12Nef properties encouraged the designing of new strategies of anti HIV-1 gene therapy we afforded by recovering an inducible lentivirus vector expressing F12Nef as the cytoplasmic domain of a transmembrane fusion protein including a selectable marker (i.e. the Nerve Growth Factor receptor) as the ecto- and transmembrane domains. As expected, the expression of such a chimeric protein resulted in a potent protection of transduced cells from the HIV-1 spread. In sum, and surprisingly enough, we generated a reagent effectively counteracting the HIV-1 replication through the combination of a slightly mutated AIDS pathogenetic factor together with a lentivirus vector, i.e. the result of artifactual modifications of the HIV-1 genome.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 1","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40850972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
The paracrine role played by interleukin-1 alpha in the testis. 白细胞介素-1在睾丸中的旁分泌作用。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-03-01 DOI: 10.2174/1568008043340026
K Svechnikov, C Petersen, T Sultana, A Wahlgren, C Zetterström, E Colón, C Bornestaf, O Söder
{"title":"The paracrine role played by interleukin-1 alpha in the testis.","authors":"K Svechnikov,&nbsp;C Petersen,&nbsp;T Sultana,&nbsp;A Wahlgren,&nbsp;C Zetterström,&nbsp;E Colón,&nbsp;C Bornestaf,&nbsp;O Söder","doi":"10.2174/1568008043340026","DOIUrl":"https://doi.org/10.2174/1568008043340026","url":null,"abstract":"<p><p>Interleukin-1alpha (IL-1alpha) plays an important role(s) in the regulation of immune and inflammatory responses. The testis is an immunologically privileged organ and the variety of effects exerted by IL-1alpha on this organ have yet to be explored in detail. The aim of the present review is to describe our current view of the paracrine role played by IL-1alpha in testicular physiology. Testicular IL-1alpha is expressed during development, primarily in Sertoli cells, appearing in rats for the first time 20 days after birth. This cytokine is microheterogeneous, consisting of three molecular species with molecular weights of 45, 24 and 17 KDa. The 17 KDa form represents mature IL-1alpha, while the 24-KDa IL-1alpha has been shown by our research group to be an alternately spliced form of the 45-KDa pro-IL-1alpha. IL-1alpha was observed to stimulate the proliferation of immature Sertoli cells with higher efficacy than FSH. IL-1alpha was also found to exert mitogenic effects both on isolated peritubular cells and germ cells. Furthermore, isoforms of IL-1alpha were seen to stimulate basal testosterone production in immature Leydig cells, but not in the corresponding adult cells. This effect involved induction of the steroidogenic acute regulatory (StAR) protein and positively regulation by p38 MAPK. Recently, we have observed positive interactions between IL-1alpha and hormones of the GH/IGF-I system that lead to enhanced androgen production by the Leydig cell. In conclusion, our findings suggest that isoforms of IL-1alpha may serve as paracrine mediators, alone or in concert with other factors, that support proper testicular cell functioning and, thereby, reproduction and fertility.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 1","pages":"67-74"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40851434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages. 利多卡因-肾上腺素和丙胺卡因- felypresin对中性粒细胞和巨噬细胞自然免疫相关功能的免疫调节。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-03-01 DOI: 10.2174/1568008043339974
Yasutaka Azuma, Kiyoshi Ohura
{"title":"Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages.","authors":"Yasutaka Azuma,&nbsp;Kiyoshi Ohura","doi":"10.2174/1568008043339974","DOIUrl":"https://doi.org/10.2174/1568008043339974","url":null,"abstract":"<p><p>There is accumulating evidence that local anesthetics have immunological properties in addition to their direct anesthetic activity. Because local anesthetics are often used together with blood vessel contraction drugs, such as epinephrine and felypressin in the clinical setting, we have examined possible abilities of both local anesthetic alone including lidocaine, mepivacaine, procaine, prilocaine and tetracaine, and local anesthetics with blood vessel contraction drugs including lidocaine with epinephrine and prilocaine with felypressin on the functions related to natural immunity in neutrophils and macrophages. In contrast, lidocaine, mepivacaine, procaine, prilocaine and tetracaine all inhibited adhesion, chemotaxis, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils and macrophages. Lidocaine with epinephrine and prilocaine with felypressin were effective in significantly inhibiting adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by neutrophils and macrophages. Interestingly, lidocaine with epinephrine potentiated the production of superoxide anion, whereas prilocaine with felypressine inhibited the production, irrespective of cells. In addition, epinephrine potentiated the production of superoxide anion, whereas epinephrine inhibited the production of hydrogen peroxide as well as lidocaine with epinephrine. This potentiation by epinephrine was not prevented by adrenergic antagonists. Furthermore, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that local anesthetics may inhibit the functions related to natural immunity in neutrophils and macrophages. In addition, lidocaine with epinephrine evidently differs from prilocaine with felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by neutrophils and macrophages.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40850973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
SHIP2: an emerging target for the treatment of type 2 diabetes mellitus. SHIP2:治疗2型糖尿病的新靶点
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2003-12-01 DOI: 10.2174/1568008033340144
James W Baumgartener
{"title":"SHIP2: an emerging target for the treatment of type 2 diabetes mellitus.","authors":"James W Baumgartener","doi":"10.2174/1568008033340144","DOIUrl":"https://doi.org/10.2174/1568008033340144","url":null,"abstract":"<p><p>With the rapid increase in the number of patients developing type 2 diabetes mellitus and the lack of optimal therapies, much focus has been placed on the insulin-signaling pathway in the discovery of novel drug targets. Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects. PI3K catalyzes the generation of phosphatidyl inositol (3,4,5) triphosphate (PIP(3)). Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis. Thus, PIP(3) is a critical mediator of insulin action. A family of phosphatidyl inositol phosphatases have been identified that counter-regulate PI3K activity by hydrolyzing PIP(3) to phosphatidyl inositol bisphosphate at either the 3' or 5' position of the inositol ring. Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance. Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients. Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects. This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"3 4","pages":"291-8"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008033340144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24132290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Protein-tyrosine phosphatase 1B as a potential drug target for obesity. 蛋白酪氨酸磷酸酶1B作为肥胖的潜在药物靶点。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2003-12-01 DOI: 10.2174/1568008033340108
Shrikrishna Dadke, Jonathan Chernoff
{"title":"Protein-tyrosine phosphatase 1B as a potential drug target for obesity.","authors":"Shrikrishna Dadke,&nbsp;Jonathan Chernoff","doi":"10.2174/1568008033340108","DOIUrl":"https://doi.org/10.2174/1568008033340108","url":null,"abstract":"<p><p>Obesity is increasing at an alarming rate and is considered by the World Health Organization as one of the top 10 epidemics worldwide. Resistance to leptin and insulin are likely to play a central role in obesity; thus, blocking inhibitors of these signaling pathways could prove useful in treating this disorder. Several lines of evidence have converged on protein tyrosine-phosphatase 1B (PTP1B) as one of the most important negative regulators of leptin as well as insulin signaling. Therefore, PTP1B appears to be a promising therapeutic candidate for the treatment of obesity. In this review, we discuss the role of PTP1B in leptin and insulin signaling, as well as its potential as a drug target in the treatment of obesity.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"3 4","pages":"299-304"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24132291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 30
Stearoyl-CoA desaturase-1 and the metabolic syndrome. 硬脂酰辅酶a去饱和酶-1与代谢综合征。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2003-12-01 DOI: 10.2174/1568008033340117
Paul Cohen, James M Ntambi, Jeffrey M Friedman
{"title":"Stearoyl-CoA desaturase-1 and the metabolic syndrome.","authors":"Paul Cohen,&nbsp;James M Ntambi,&nbsp;Jeffrey M Friedman","doi":"10.2174/1568008033340117","DOIUrl":"https://doi.org/10.2174/1568008033340117","url":null,"abstract":"<p><p>The incidence of obesity has increased dramatically in recent years, making it one of the most pressing public health concerns worldwide. Obesity is commonly associated with comorbid conditions, most notably diabetes, coronary artery disease, and hypertension, and the coexistence of these diseases has been termed the Metabolic Syndrome. The identification of the hormone leptin provided a molecular link to obesity. Leptin is recognized as the central mediator in an endocrine circuit regulating energy homeostasis. Leptin administration leads to hypophagia, increased energy expenditure, and weight loss, while leptin deficiency enacts an adaptive response to starvation manifested by hyperphagia, decreased energy expenditure, and suppression of the neuroendocrine axis. While elucidation of leptin's role has permitted a more detailed view of the biology underlying energy homeostasis, most obese individuals are leptin resistant. A more complete understanding of the molecular components of the leptin pathway is necessary to develop effective treatment for obesity and the Metabolic Syndrome. The identification and role of one such component, stearoyl-CoA desaturase-1 (SCD-1), is reviewed here. Leptin's actions are not due to its anorectic effects alone. Leptin also mediates specific metabolic effects, including the potent depletion of triglyceride from liver and other peripheral tissues. To explore the molecular basis by which leptin depletes hepatic lipid, we used oligonucleotide arrays to identify genes in liver whose expression was modulated by leptin treatment. An algorithm was created that identified and ranked genes specifically repressed by leptin. The gene ranking at the top of this list was SCD-1, the rate limiting enzyme in the biosynthesis of monounsaturated fats. SCD-1 was specifically repressed during leptin-mediated weight loss, and mice lacking SCD-1 showed markedly reduced adiposity on both a lean and ob/ob background (ab(J)/ab(J); ob/ob), despite higher food intake. ab(J)/ab(J); ob/ob mice also showed a complete correction of the hypometabolic phenotype and hepatic steatosis of ob/ob mice, suggesting that fatty acid oxidation is enhanced in the absence of SCD-1. These findings indicate that pharmacologic manipulation of SCD-1 may be of benefit in the treatment of obesity, diabetes, hepatic steatosis, and other components of the Metabolic Syndrome.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"3 4","pages":"271-80"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008033340117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24133531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 100
DGAT: novel therapeutic target for obesity and type 2 diabetes mellitus. DGAT:治疗肥胖和2型糖尿病的新靶点。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2003-12-01 DOI: 10.2174/1568008033340081
Angela Subauste, Charles F Burant
{"title":"DGAT: novel therapeutic target for obesity and type 2 diabetes mellitus.","authors":"Angela Subauste,&nbsp;Charles F Burant","doi":"10.2174/1568008033340081","DOIUrl":"https://doi.org/10.2174/1568008033340081","url":null,"abstract":"<p><p>Obesity is currently an exceptionally common problem in humans. The last several years have produced a significant number of breakthroughs in obesity related areas of investigation. Triglycerides are considered the main form of storage of excess calories in fat. A key enzyme in the synthesis of triglycerides is acylCoA: diacylglycerol acyltransferase (DGAT). Recent studies have shown that mice deficient in this enzyme are resistant to diet induced obesity and have increased insulin and leptin sensitivity. These effects suggest that inhibition of DGAT in vivo may be a novel therapeutic target not only for obesity but also for diabetes.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"3 4","pages":"263-70"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24133530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 28
Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. 脂联素/Acrp30在体内作为抗糖尿病和抗动脉粥样硬化脂肪因子的双重作用。
Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2003-12-01 DOI: 10.2174/1568008033340090
Toshimasa Yamauchi, Kazuo Hara, Naoto Kubota, Yasuo Terauchi, Kazuyuki Tobe, Philippe Froguel, Ryozo Nagai, Takashi Kadowaki
{"title":"Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine.","authors":"Toshimasa Yamauchi,&nbsp;Kazuo Hara,&nbsp;Naoto Kubota,&nbsp;Yasuo Terauchi,&nbsp;Kazuyuki Tobe,&nbsp;Philippe Froguel,&nbsp;Ryozo Nagai,&nbsp;Takashi Kadowaki","doi":"10.2174/1568008033340090","DOIUrl":"https://doi.org/10.2174/1568008033340090","url":null,"abstract":"<p><p>Genome-wide scanning is a powerful tool to identify susceptible chromosome loci, however, individual chromosomal regions still have many candidate genes. Although cDNA microarray analysis provides valuable information for identifying genes involved in pathogenesis, expression levels of many genes are changed. A novel approach for identification of therapeutic targets is the combination of genome-wide scanning and the use of DNA chips, as shown in Fig. (1). Using DNA chips, we screened for secreted molecules, the expressions of which were changed in adipose tissues from mice rendered insulin resistance. Decreased expression of one of these molecules, adiponectin/Acrp30, correlates strongly with insulin resistance. Interestingly, recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where adiponectin gene is located. Decreasing serum adiponectin levels are associated with increased risk for type 2 diabetes. Interestingly, adiponectin was decreased in insulin resistant rodent models both of obesity and lipoatrophy, and replenishment of adiponectin ameliorated their insulin resistance. Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes Adiponectin knockout mice showed insulin resistance and glucose intolerance. In muscle and liver, adiponectin activated AMP kinase and PPARalpha pathways thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated insulin resistance under a high-fat diet. Despite similar plasma glucose and lipid levels on an apoE deficient background, adiponectin transgenic apoE deficient mice showed amelioration of atherosclerosis, which was associated with decreased expressions of class A scavenger receptor and tumor necrosis factor alpha. Finally, cDNA encoding adiponectin receptors (AdipoR1 and R2) have been identified by expression cloning, which facilitates the understanding of molecular mechanisms of adiponectin actions and obesity-linked diseases such as diabetes and atherosclerosis and the designing of novel antidiabetic and anti-atherogenic drugs with AdipoR1 and R2 as molecular targets.</p>","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"3 4","pages":"243-54"},"PeriodicalIF":0.0,"publicationDate":"2003-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24133528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 147
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信