Abstract：
:Insulin signaling plays a physiological role in traditional insulin target tissues controlling glucose homeostasis as well as in pancreatic β-cells and in the endothelium. Insulin signaling abnormalities may, therefore, be pathogenic for insulin resistance, impaired insulin secretion, endothelial dysfunction, and eventually, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Tribbles homolog 3 (TRIB3) is a 45-kDa pseudokinase binding to and inhibiting Akt, a key mediator of insulin signaling. Akt-mediated effects of TRIB3 in the liver, pancreatic β-cells, and skeletal muscle result in impaired glucose homeostasis. TRIB3 effects are also modulated by its direct interaction with other signaling molecules. In humans, TRIB3 overactivity, due to TRIB3 overexpression or to Q84R genetic polymorphism, with R84 being a gain-of-function variant, may be involved in shaping the risk of insulin resistance, T2DM, and cardiovascular disease. TRIB3 overexpression has been observed in the liver, adipose tissue, skeletal muscle, and pancreatic β-cells of individuals with insulin resistance and/or T2DM. The R84 variant has also proved to be associated with insulin resistance, T2DM, and cardiovascular disease. TRIB3 direct effects on the endothelium might also play a role in increasing the risk of atherosclerosis, as indicated by studies on human endothelial cells carrying the R84 variant that are dysfunctional in terms of Akt activation, NO production, and other proatherogenic changes. In conclusion, studies on TRIB3 have unraveled new molecular mechanisms underlying metabolic and cardiovascular abnormalities. Additional investigations are needed to verify whether such acquired knowledge will be relevant for improving care delivery to patients with metabolic and cardiovascular alterations.
journal_name
Endocr Revjournal_title
Endocrine reviewsauthors
Prudente S,Sesti G,Pandolfi A,Andreozzi F,Consoli A,Trischitta Vdoi
10.1210/er.2011-1042subject
Has Abstractpub_date
2012-08-01 00:00:00pages
526-46issue
4eissn
0163-769Xissn
1945-7189pii
er.2011-1042journal_volume
33pub_type
杂志文章,评审abstract：:The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs p...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv.21.1.0389
更新日期：2000-02-01 00:00:00
abstract：:In human beings, two forms of GnRH, termed GnRH-I and GnRH-II, encoded by separate genes have been identified. Although these hormones share comparable cDNA and genomic structures, their tissue distribution and regulation of gene expression are significantly dissimilar. The actions of GnRH are mediated by the GnRH rec...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2003-0039
更新日期：2005-04-01 00:00:00
abstract：:Members of the TGF-beta superfamily, which includes TGF-betas, growth differentiation factors, bone morphogenetic proteins, activins, inhibins, and glial cell line-derived neurotrophic factor, are synthesized as prepropeptide precursors and then processed and secreted as homodimers or heterodimers. Most ligands of the...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0003
更新日期：2002-12-01 00:00:00
abstract：:Breast cancer, the second most common cause of cancer-related deaths in American women, varies substantially in incidence and mortality according to race and ethnicity in the United States. Although the overall incidence of breast cancer among African-American (AA) women is lower than in white American women, this can...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2006-0019
更新日期：2007-12-01 00:00:00
abstract：:Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms a...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0012
更新日期：2003-02-01 00:00:00
abstract：:There is a large body of literature showing that prolactin (PRL) exerts growth-promoting activities in breast cancer, and possibly in prostate cancer and prostate hyperplasia. In addition, increasing evidence argues for the involvement of locally produced (autocrine) PRL, perhaps even more than pituitary-secreted (end...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2004-0016
更新日期：2005-05-01 00:00:00
abstract：:Cells from the chorionic girdle of the equine trophoblast invade the maternal endometrium at day 36 of gestation and become established as secretory elements known as the endometrial cups. These structures, which persist for 40-60 days, produce a gonadotropin which can be found in circulation until about day 130 of ge...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-12-1-27
更新日期：1991-02-01 00:00:00
abstract：:To allow selection of embryos for transfer after in vitro fertilization, ovarian stimulation is usually carried out with exogenous gonadotropins. To compensate for changes induced by stimulation, GnRH analog cotreatment, oral contraceptive pretreatment, late follicular phase human chorionic gonadotropin, and luteal ph...
journal_title：Endocrine reviews
pub_type： 历史文章,杂志文章,评审
doi：10.1210/er.2005-0015
更新日期：2006-04-01 00:00:00
abstract：:Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transc...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2005-0018
更新日期：2006-06-01 00:00:00
abstract：:This paper has reviewed current knowledge of clinical, biochemical, and morphological manifestations of extracranial GRH-producing tumors. Excessive GRH release stimulates pituitary somatotrophs causing elevation of blood GH levels and acromegaly. In some patients with GRH-containing tumor, blood GH concentrations are...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-9-3-357
更新日期：1988-08-01 00:00:00
abstract：:Normal reproductive function in mammals requires precise control of LH synthesis and secretion by gonadotropes of the anterior pituitary. Synthesis of LH requires expression of two genes [alpha-glycoprotein subunit (alphaGSU) and LHbeta] located on different chromosomes. Hormones from the hypothalamus and gonads modul...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2003-0029
更新日期：2004-08-01 00:00:00
abstract：:Many hormones, growth factors, and cytokines regulate proliferation of their target cells. Perhaps the most universal signaling cascades required for proliferative responses are those initiated by transient rises in intracellular calcium (Ca(2+)). The major intracellular receptor for Ca(2+) is calmodulin (CaM). CaM is...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2003-0008
更新日期：2003-12-01 00:00:00
abstract：:In humans and other mammalian species, the pool of resting primordial follicles serves as the source of developing follicles and fertilizable ova for the entire length of female reproductive life. One question that has intrigued biologists is: what are the mechanisms controlling the activation of dormant primordial fo...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2008-0048
更新日期：2009-08-01 00:00:00
abstract：:The ovary and uterus undergo extensive tissue remodeling throughout each reproductive cycle. This remodeling of the extracellular environment is dependent upon the cyclic hormonal changes associated with each estrous or menstrual cycle. In the ovary, tissue remodeling is requisite for growth and expansion of the folli...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0005
更新日期：2003-08-01 00:00:00
abstract：:Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic pepti...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2005-0014
更新日期：2006-02-01 00:00:00
abstract：:The most active corticosteroids are 11 beta-hydroxylated. Humans have two isozymes with 11 beta-hydroxylase activity that are respectively required for cortisol and aldosterone synthesis. CYP11B1 (11 beta-hydroxylase) is expressed at high levels and is regulated by ACTH, whereas CYP11B2 (aldosterone synthase) is norma...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-15-4-421
更新日期：1994-08-01 00:00:00
abstract：:Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linki...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0010
更新日期：2003-06-01 00:00:00
abstract：:The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basi...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/edrv-14-1-107
更新日期：1993-02-01 00:00:00
abstract：:Bile acids derived from cholesterol and oxysterols derived from cholesterol and bile acid synthesis pathways are signaling molecules that regulate cholesterol homeostasis in mammals. Many nuclear receptors play pivotal roles in the regulation of bile acid and cholesterol metabolism. Bile acids activate the farnesoid X...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2000-0035
更新日期：2002-08-01 00:00:00
abstract：:Skeletal homeostasis is determined by systemic hormones and local factors. Bone morphogenetic proteins (BMP) are unique because they induce the differentiation of mesenchymal cells toward cells of the osteoblastic lineage and also enhance the differentiated function of the osteoblast. However, the activity of BMPs nee...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0023
更新日期：2003-04-01 00:00:00
abstract：:Ovarian steroids normally exert homeostatic negative feedback on GnRH release. During sustained exposure to elevated estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of estradiol switches to positive, inducing a surge of GnRH release from the brain, which signals the pitui...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2009-0023
更新日期：2010-08-01 00:00:00
abstract：:Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2001-0034
更新日期：2005-12-01 00:00:00
abstract：:Disruption of the GH receptor (GHR) gene eliminates GH-induced intracellular signaling and, thus, its biological actions. Therefore, the GHR gene disrupted mouse (GHR-/-) has been and is a valuable tool for helping to define various parameters of GH physiology. Since its creation in 1995, this mouse strain has been us...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2010-0009
更新日期：2011-06-01 00:00:00
abstract：:Spermatogenesis is the process by which a single spermatogonium develops into 256 spermatozoa, one of which will fertilize the ovum. Since the 1950s when the stages of the epithelial cycle were first described, reproductive biologists have been in pursuit of one question: How can a spermatogonium traverse the epitheli...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2003-0022
更新日期：2004-10-01 00:00:00
abstract：:In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not fe...
journal_title：Endocrine reviews
pub_type： 杂志文章
doi：10.1210/endrev/bnaa020
更新日期：2020-12-01 00:00:00
abstract：:Gut hormones signal to the central nervous system to influence energy homeostasis. Evidence supports the existence of a system in the gut that senses the presence of food in the gastrointestinal tract and signals to the brain via neural and endocrine mechanisms to regulate short-term appetite and satiety. Recent evide...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2006-0028
更新日期：2006-12-01 00:00:00
abstract：:Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to emerge from autoimmunity occurring in the thyroid gland, most frequently in Graves disease (GD). It is disfiguring and potentially blinding, culminating in orbital tissue remodeling and disruption of function of structures adjacent to the...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2018-00066
更新日期：2019-02-01 00:00:00
abstract：:During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These ob...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2002-0019
更新日期：2003-10-01 00:00:00
abstract：OBJECTIVE:To summarize controlled trials examining the effect of calcium on bone density and fractures in postmenopausal women. DATA SOURCE:We searched MEDLINE and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we examined citations of relevant articles and proceedings of international meetings...
journal_title：Endocrine reviews
pub_type： 杂志文章,meta分析,评审
doi：10.1210/er.2001-7002
更新日期：2002-08-01 00:00:00
abstract：:The endocrine functions of the adipose organ are widely studied at this stage. The adipose organ, and in particular adipocytes, communicate with almost all other organs. Although some adipose tissue pads assume the functions as distinct "miniorgans," adipocytes can also be present in smaller numbers interspersed with ...
journal_title：Endocrine reviews
pub_type： 杂志文章,评审
doi：10.1210/er.2006-0033
更新日期：2006-12-01 00:00:00
