TCF7L2基因与2型糖尿病

转录因子7类似物2(TCF7L2)常见变异在不同的种族中几乎都与2型糖尿病显著相关.TCF7L2剪接有显著的组织特异性,在2型糖尿病患者的胰岛内TCF7L2 mRNA水平增高.其变异与胰岛素分泌功能减退有关,机制可能是其特异性损害肠促胰素(incretin)如胰高血糖素样肽-1(GLP-1)诱导的胰岛素分泌,也可能因胰岛素原向胰岛素的转换异常,和(或)参与Wnt信号通路的激活而致2型糖尿病.因此对2型糖尿病致病基因TCF7L2基因的研究有助于揭示糖尿病的发病机制、病理生理及为糖尿病的治疗提供新的靶点.     

高同型半胱氨酸血症与脂肪功能异常

近年来,2型糖尿病、肥胖的发病率在我国急剧增加,并且趋于年轻化,已经成为严重威胁人民健康的重要疾病.脂肪功能异常出现于肥胖的早期阶段,是肥胖患者发生代谢异常及心脑血管疾病的重要机制[1-2].高同型半胱氨酸血症作为动脉粥样硬化的独立危险因素,在我国的发病率处于较高水平[3].研究显示,同型半胱氨酸（Hcy）可通过多条途径导致脂肪功能异常,进而引发机体慢性炎症状态及胰岛素抵抗[4-5].现就同型半胱氨酸与脂肪功能异常的相关机制及最新研究进展作一阐述.     

睾酮与男性代谢综合征

男性血清睾酮水平与代谢综合征的发生、发展密切相关.低睾酮水平可能导致腹型肥胖、糖代谢异常、血脂紊乱及高血压,给予睾酮水平低下者睾酮替代治疗(TRT)能明显改善其相关代谢指标.同时,腹型肥胖、糖代谢异常也可通过抑制Leydig细胞功能、增加芳香化酶活性等引起睾酮水平下降.     

α-硫辛酸联合胰岛素强化治疗对初诊2型糖尿病患者的疗效观察

目的 观察α-硫辛酸联合胰岛素泵强化降糖治疗对初诊2型糖尿病患者胰岛β细胞功能的保护作用.方法 对空腹血糖≥9.0 mmol/L和(或)餐后2小时血糖≥14.0 mmol/L的50例初诊2型糖尿病患者进行为期2周的α-硫辛酸联合胰岛素泵强化治疗,比较治疗后血糖、口服葡萄糖耐量试验(OGTT)胰岛素及C肽分泌值、超敏C反应蛋白(hs-CRP)和胰岛β细胞功能等.结果 2用的强化治疗显示出确切的降糖效果,联合治疗组呈现出更好的β细胞功能状态,出现了明显增加的胰岛素、C肽分泌相(P＜0.01),胰岛β细胞功能明显改善(P＜0.01),hs-CRP值明显下降(P＜0.01).结论 初诊2型糖尿病患者采用α-硫辛酸联合胰岛素泵强化治疗,能显著改善炎症状态,恢复胰岛β细胞功能.     

新一代药物GLP-1类似物对2型糖尿病患者β细胞功能的保护

2型糖尿病以β细胞功能进行性减退和β细胞量的减少为特点.高血糖、炎性因子和游离脂肪酸等与肥胖、胰岛素抵抗及β细胞凋亡密切相关.保护β细胞、针对β细胞功能减退的治疗是2型糖尿病治疗的关键.胰高血糖素样肽1(GLP-1)是肠道促胰岛激素,它的多重生物学效应可以改善2型糖尿病的病理生理学状况.GLP-1对血糖的良好控制以及对B细胞功能的改善作用使其备受瞩目.本文围绕2型糖尿病发病的重要环节--β细胞功能,阐述了β细胞功能减退和β细胞量减少的机制,并综述了GLP-1保护β细胞功能和增加β细胞量的研究进展.     

白细胞介素-6受体基因多态性与内分泌疾病的关系

白细胞介素-6(IL-6)是由不同种类细胞如淋巴细胞、内皮细胞、成纤维细胞、骨骼肌细胞及脂肪细胞所分泌的一种多效性细胞因子,主要参与糖代谢和脂代谢,IL-6水平与肥胖和2型糖尿病相关.IL-6发挥其生物学功能是通过结合白细胞介素-6受体(Ⅱ-6R)的双链系统(gp80、gp130)来完成的.IL-6R基因的外显子和内含子中均存在单核苷酸多态性(SNPs),IL-6R基因的SNPs与2型糖尿病、肥胖、雄激素过多症和多囊卵巢综合征等代谢性疾病具有相关性.     

2型糖尿病与炎症及他汀类药物

2型糖尿病发病中心环节是胰岛素抵抗和胰岛β细胞的功能缺陷.胰岛素抵抗贯穿在2型糖尿病的发生、发展的全过程.β细胞功能缺陷是发病必要条件.胰岛素抵抗常合并一系列心血管危险因素,如:高血糖,高血压,高血脂,肥胖,多种心血管危险因素"聚集"现象又称为"代谢综合征".这些症候群的表现归结到底,均有内皮细胞功能紊乱以及动脉粥样硬化(AS).随着对2型糖尿病、胰岛素抵抗(IR)以及动脉粥样硬化(AS)本质的认识不断深化研究结果,发现了氧化应激、炎症反应机制参与了IR与内皮功能紊乱,并将IR、胰岛B细胞功能减退与代谢综合征及心血管并发症联系在一起,炎症反应成为其"共同的土壤".     

肥胖与内皮细胞损伤的关系和相关机制研究进展

肥胖与内皮细胞损害密切相关,肥胖者的内皮依赖性及非依赖性的血管舒张功能均明显降低,并有炎性因子的异常。肥胖时存在的内皮胰岛素抵抗、脂代谢紊乱、氧化应激增强和脂肪组织分泌细胞因子如肿瘤坏死因子-α、白细胞介素-6、瘦素、脂联素、抵抗素的异常均可能为肥胖致内皮损伤的机制。防治肥胖2型糖尿病患者的心血管并发症时,积极减轻体重比严格控制血糖更为重要。     

单纯性肥胖老年人糖耐量与血清脂联素、炎性因子相关性研究

60名单纯性肥胖老年人(65~85岁),另选择体重正常中老年人20名作为对照组,采用2小时口服糖耐量试验,胰岛素和C肽,空腹APN、高敏C反应蛋白(Hs-CRP)、肿瘤坏死因子(TNF-α)。胰岛素抵抗用胰岛素抵抗指数来评价,β细胞功能用注射葡萄糖30分钟前后的胰岛素和血糖变化(I30-I0/G30-G0)来评价。结果单纯性肥胖组13.33%存在糖耐量受损,8.33%患有2型糖尿病。糖耐量受损人群在糖负荷后胰岛素和C肽水平有所下降,而2型糖尿病老年人胰岛素和C肽水平进一步下降,30分钟胰岛素变化与血糖变化的比是下降的。胰岛素抵抗在糖耐量受损人群中是显著存在的。IGT及T2DM组TPN水平显著低于对照组及NGT组,Hs-CRP、TNF-α水平相反。结论在本地区单纯性肥胖老年人中,糖耐量受损高度流行,APN在肥胖及糖尿病发病过程中具有保护作用,细胞炎性因子表达异常是肥胖和糖尿病的独立危险因素。     

MIN6细胞系的细胞学特性及其应用

MIN6细胞系是从表达类人猿病毒40大T抗原(受胰岛毒启动子控制)的转基因非肥胖糖尿病小鼠胰岛瘤中建立的,其内分泌功能与胰腺组织非常接近,是研究胰岛细胞功能的理想模型.MIN6细胞系可用于胰腺分泌的研究,β细胞的适宜刺激信号的探索;1型糖尿病发病机制的研究;氧化应激、自噬、游离脂肪酸对2型糖尿病发病的影响;在胰腺移植后发生排斥的机制研究.     

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.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.