脂肪细胞因子与胰岛素抵抗

脂肪细胞因子是指从脂肪组织分离的生物活性分子,包括细胞因子、生长因子、炎性蛋白等,与肥胖、胰岛素抵抗等密切相关.胰岛素与靶细胞膜上特异受体结合后发挥正常的信号转导作用,而该转导途径直接或者间接地受大部分脂肪细胞因子的负件调节,导致机体出现胰岛素抵抗及其相父疾病.本文综述了胰岛素信号转导作用、代谢综合征患者血浆脂肪细胞因子水平的变化以及脂肪细胞因子调节胰岛素信号转导的机制.     

Visfatin与糖尿病及肥胖关系的研究进展

内脂素(visfatin)作为一种新发现的主要由内脏脂肪组织分泌的脂肪因子,在糖尿病患者及肥胖者血浆及内脏脂肪中的表达明显增高.Visfatin与胰岛素受体结合,激活其下游信号转导蛋白以刺激胰岛素信号转导,具有类胰岛素作用,可显著降低血糖,且其作用不受进食的影响.其异常表达在肥胖与糖尿病的发病过程中可能起重要作用.     

内脂素研究进展

内脂素是一种主要由内脏脂肪分泌的细胞因子,通过与胰岛素受体结合发挥类胰岛素样的降血糖作用,并促进脂肪组织的分化与合成。有研究认为内脂素由于结构缺陷可能并非真正具类胰岛素样作用。尽管如此,内脂素仍为肥胖和糖尿病治疗提供可能靶点。     

Visfatin研究进展

Visfatin是新发现的由内脏脂肪细胞分泌的一种脂肪细胞因子,可结合并激活胰岛素受体,模拟胰岛素作用,从而降低血糖;还能够促进脂肪组织的分化、合成及积聚。而对于visfatin与胰岛素抵抗之间的关系目前仍不清楚。现有研究表明visfatin可能是联系肥胖和糖尿病之间的未知环节,它的发现为研究肥胖和糖尿病的发病机制增加了新内容,可能为糖尿病治疗提供一个新的靶点。     

视黄醇结合蛋白4与多囊卵巢综合征及妊娠糖尿病

视黄醇结合蛋白4主要由肝脏合成,是血液中一种运送视黄醇的结合蚩白,亦是脂肪组织分泌的一种脂肪细胞因子.小鼠实验发现,其在组织中的过度表达可使磷脂酰肌醇3激酶活性下降,胰岛素受体底物1酪氨酸磷酸化降低.可能与胰岛素抵抗的发生有关.肥胖、糖耐量减低、胰岛素抵抗、多囊卵巢综合征、妊娠糖尿病患者血清中视黄醇结合蛋白4含量与正常者相比升高,其可能与此类疾病的发病机制有关.     

内脏脂肪素——一种能模拟胰岛素作用的新脂肪细胞因子

研究人员最近发现了一种新脂肪细胞因子——内脏脂肪素(visfatin)，其具有很好的类胰岛素活性，能够通过与胰岛素受体结合激活胰岛素信号通道，从而降低血糖。目前科学家对其在机体中的具体作用还不清楚，进一步研究有可能为糖尿病的研究和治疗开辟新途径。日本研究人员Fukuhara等发现visfatin主要在人类和小鼠的腹部内脏脂肪中表达，在肥胖发展过程中其血浆浓度升高。     

脂肪细胞因子Sfrp5的研究进展

分泌型卷曲相关蛋白5(Sfrp5)是分泌型卷曲相关蛋白家族(Sfrs)的一员,作为Wnt信号通路的抑制剂,可通过调控Wnt信号转导通路参与胚胎发育、细胞增殖及肿瘤生成等过程.最近研究表明Sfrp5是一种脂肪细胞因子,前体脂肪细胞分化成熟过程中被强烈诱导表达;其也可通过阻断脂肪组织Wnt信号通路,促进脂肪细胞分化,增加饮食诱导的肥胖.Sfrp5表达水平与肥胖和糖尿病相关,通过减弱非经典Wnt信号转导通路而减轻机体胰岛素抵抗.深入研究Sfrp5的生物学功能,将为治疗肥胖及相关代谢性疾病提供新的机会.     

visfatin与2型糖尿病

visfatin是在人和小鼠的内脏脂肪中提取出的一种新的脂肪细胞因子,它可以结合并激活胰岛素受体,模拟胰岛素的作用,降低血糖水平,改善胰岛素抵抗。糖尿病的患病人数逐年增加,糖尿病已经成为一个新的流行性疾病。现发现visfatin与糖尿病关系密切,本文将visfatin的结构及在体内的分布以及visfatin与胰岛素受体、血糖水平和胰岛素抵抗和脂代谢紊乱的关系作一综述。     

新的脂肪细胞因子与糖尿病肾病

Chemerin、visfatin、vaspin、视黄醇结合蛋白 4(RBP4 )是近几年新发现的脂肪细胞因子,它们参与体内物质和能量代谢、肥胖、胰岛素抵抗等病理生理过程. 目前许多研究发现,它们与糖尿病肾病关系密切,直接或间接参与了糖尿病肾病的病理生理过程.对这几种因子的深入研究将为糖尿病肾病的防治提供新的预测指标及治疗靶点.     

白细胞介素-6与胰岛素抵抗

低水平的炎症状态是胰岛素抵抗的病因之一,白细胞介素(IL)-6作为一种炎症介质,参与了胰岛素抵抗的发生和发展。IL-6导致胰岛素抵抗的主要机制有:(1)IL-6与受体结合直接或通过诱导产生细胞因子信号转导抑制因子-3,间接作用于胰岛素信号转导系统,干扰胰岛素信号转导,降低胰岛素敏感性。(2)影响脂代谢及脂肪因子,降低胰岛素的作用。生活方式的干预和药物治疗可降低血浆IL-6水平,改善胰岛素抵抗。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.