胰岛素样生长因子-1与糖尿病及其并发症的关系

目前，有关胰岛素生长因子-1（IGF-1）在糖尿病中的作用及其机制的研究成为医学界关注的焦点，它参与糖尿病并发症的发生、发展，在糖尿病的发病及治疗方面发挥了重要作用。IGF-1的类胰岛素样作用使其在糖尿病的治疗中有着较好的应用前景。现就与糖尿病及其并发症的关系综述如下。     

环境内分泌干扰物与糖尿病关系的研究进展

环境内分泌干扰物是指具有潜在的干扰内分泌系统功能的外源性物质,包括多卤芳香烃类、烷基酚、有机氯杀虫剂和除草剂、二英和重金属等。它们不仅能影响人类和动物的生殖、免疫和神经系统,也可以干扰胰岛β细胞的生理功能,促进细胞凋亡,诱发胰岛素抵抗,最终导致糖尿病。确定致糖尿病性环境内分泌干扰物的种类,明确其作用机制,对糖尿病的防治具有重要意义。     

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目前糖尿病正越来越广泛地在世界范围内流行,而癌症作为一种严重影响人类健康的疾病,发病率也逐年增高。糖尿病通过高胰岛素血症、肥胖等普遍性机制以及一些器官特异性机制与恶性肿瘤发生关联,显著增加了多种癌症的发生率、病死率,并影响其预后及对辅助治疗的反应。抗糖尿病药对肿瘤发生发展的不同影响以及新兴抗癌药对血糖和胰岛素的作用也逐渐被揭开面纱。然而,目前糖尿病与恶性肿瘤关系的具体机制还存在许多不明之处,值得进行更多更完善的研究来进一步探讨两者的关系,以起到更好的疾病防治作用。     

医源性胰岛素的心血管非治疗作用

医源性高胰岛素血症常见于使用大剂量外源性胰岛素,以获得接近正常血糖浓度的糖尿病患者,尤以2型糖尿病伴肥胖、胰岛素用量偏大者常见。随着研究的深入,高浓度胰岛素的心血管非治疗作用越来越引起研究人员的关注,现对医源性高胰岛素血症的心血管非治疗作用进行综述,并总结其可能的作用机制。     

过氧化物酶体增殖物激活受体激动剂对糖尿病肾病保护作用及机制的研究进展

PPAR-γ激动剂作为胰岛素增敏剂除能降低血糖及增加胰岛素敏感性外,还在脂质代谢、抑制细胞因子、抗炎、免疫调节和血压调节等方面起着关键作用。近来研究发现过氧化物酶体增殖物激活受体激动剂对糖尿病肾病有一定的保护作用,本文就其对糖尿病肾病保护作用及机制简要综述。     

地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素治疗2型糖尿病的疗效观察

目的探讨地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素对2型糖尿病患者的疗效。方法90例2型糖尿病患者分别应用地特胰岛素、甘精胰岛素与中性鱼精蛋白锌胰岛素联合短效胰岛素治疗,比较3组治疗前后空腹血糖、餐后2h血糖、胰岛素用量及低血糖发生率。结果3组血糖均下降,但地特胰岛素组降糖效果更明显,且低血糖发生率低。结论与甘精胰岛素、中性鱼精蛋白锌胰岛素相比,地特胰岛素治疗新诊断的2型糖尿病疗效更好,低血糖发生率较低。     

大黄酸改善胰岛素敏感性的作用及其机制研究

改善胰岛素敏感性对防治2型糖尿病(T2DM)有重要意义.我国中医药治疗糖尿病效果显著但机制尚不甚清楚,本课题组从改善胰岛素敏感性的角度入手,先后通过药物筛选、细胞和动物实验3个部分研究中药大黄单体成分--大黄酸对糖尿病的治疗作用,其机制可能与上调机体外周组织的过氧化物酶体增殖物活化受体(PPAR)-慵捌咸烟亲说鞍?GLUT)表达,从而促进外周组织葡萄糖摄取并改善机体胰岛素敏感性有关.本文将分别对这3部分实验内容进行介绍并就大黄酸改善胰岛素敏感性的作用机制展开讨论.     

锌转运体8及其自身抗体

锌是胰岛素储存和分泌机制中的一个重要组分,β细胞需要有效且特异的转运体来累积足够量的锌.锌转运体8(ZnT8)是新近发现的一种1型糖尿病自身抗原,具有高度β细胞特异性,通过影响锌离子浓度而在胰岛素合成和分泌中发挥重要作用.ZnT8自身抗体对自身免疫性糖尿病(尤其对其他自身抗体阴性者)有着重要的诊断与预测价值.ZnT8基因(SLC30A8基因)多态性影响ZnT8自身抗体的特异性.     

炎症与2型糖尿病

2型糖尿病的发病机制主要是胰岛素抵抗和胰岛素分泌不足。但近来的研究发现许多炎症因子与糖尿病及其并发症有一定关联,慢性炎症反应在2型糖尿病发生、发展中的作用越来越受到人们的重视。     

肝源性糖尿病诊疗进展

肝源性糖尿病(HD)作为一种继发于肝细胞损伤及肝纤维化基础上的综合征,表现为显著升高的血糖、生长激素、胰岛素样生长因子、游离脂肪酸及细胞因子等。近年来,由于HD发病率的上升,越来越多的研究表明其发病机制与胰岛素抵抗和肝炎病毒对胰腺细胞的破坏等密切相关,本文将综述肝源性糖尿病的最新发病机制和诊疗进展。     

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.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

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.