妊娠期大鼠胰岛β细胞适应性变化的研究

目的 探讨大鼠妊娠期胰岛β细胞的变化节律.方法 采用口服糖耐量试验、胰岛素释放试验以及大鼠胰岛对葡萄糖刺激下的胰岛素分泌试验研究大鼠妊娠期胰岛β细胞的功能改变特点.并用5-溴尿脱氧嘧啶核苷(BrdU)标记和抗胰岛素抗体免疫组化双染法研究大鼠妊娠期胰岛β细胞增殖的变化.结果 与正常对照组相比,大鼠妊娠期表现出空腹血糖减低的趋势,但未出现糖耐量的异常.与此同时,糖负荷后胰岛素的分泌从孕14.5 d开始增强并持续至孕20.5 d.体外胰岛β细胞的分泌能力则从孕12.5 d开始显著增强直至孕20.5 d.此外,大鼠妊娠期胰岛β细胞的增殖指数(PI)从孕12.5 d开始显著升高,孕14.5 d达到高峰.大鼠妊娠期胰岛β细胞的面积亦明显高于正常水平.结论 大鼠妊娠期胰岛β细胞的功能和增殖均发生了改变,从孕12.5 d开始增强,孕中晚期变化最为显著,并持续至孕20.5 d.     

钙离子对葡萄糖、亮氨酸、KIC刺激离体培养大鼠胰岛株释放胰岛素及~(65)Zn的影响

本实验以大鼠胰岛株培养方法证明:(1)高浓度葡萄糖、亮氨酸或KIC加IBMX在细胞外液中有钙离子存在时,方能刺激胰岛迅速释放胰岛素和~(65)Zn;(2)葡萄糖、亮氨酸或KIC在一定的高浓度条件下,方能刺激胰岛释放胰岛素和~(65)Zn明显增加;(3)大鼠胰岛在高浓度葡萄糖、亮氨酸或KIC的刺激下,~(65)Zn的释放量明显高于胰岛素的释放量。因此,可以认为胰岛中的锌,大部分存在于B细胞非颗粒部分,它对某些促分泌物质的释放反应较胰岛素的释放反应更为敏感。     

妊娠期胰岛素抵抗与妊娠糖尿病

妊娠期胰岛素抵抗 (IR)是出现于妊娠晚期的代谢变化 ,妊娠期IR对妊娠妇女的糖代谢、脂肪代谢及蛋白质代谢都有明显的影响 ,主要表现为对葡萄糖摄取和氧化减少、脂肪的分解和氧化增加、蛋白质的分解利用减少。妊娠期IR及潜在的胰岛 β细胞功能不足是妊娠糖尿病 (GDM)的发病机制。GDM与 2型糖尿病 (T2DM)、代谢综合征有着相同的发病基础 ,GDM妇女的高血压、T2DM发病率明显高于正常人群。     

胃旁路术减肥同时改善糖代谢的机制

胃旁路术在平稳减肥的同时能增加胰岛素敏感性,改善糖代谢紊乱。其机制包括胃减容以减少摄入,前肠旁路致胃肠-胰岛轴改变引起多种胃肠激素如ghrelin、胰升糖素样肽-1（GLP-1）、葡萄糖依赖性促胰岛素多肽、多肽YY等变化改善了胰岛素的分泌和（或）活性,脂肪细胞因子的改变如脂联素水平升高、瘦素及酰化刺激蛋白降低和一些炎性反应因子如C反应蛋白、白细胞介素-6（IL-6）的变化等。     

长期高浓度葡萄糖对胰岛细胞凋亡和功能相关基因表达的影响

目的　探明长期高浓度葡萄糖对体外胰岛细胞功能和凋亡相关基因表达的影响。方法应用放免法检测不同浓度葡萄糖培养后大鼠胰岛细胞和小鼠 βTc3细胞在葡萄糖刺激时培育上清液和细胞内的胰岛素水平 ;应用半定量多重RT PCR和Northern印迹法检测培养后IDX 1(Isletduodenalhomeobox 1) ,葡萄糖激酶 (GK ) ,葡萄糖转运子 2 (GLUT2 ) ,C/EBPβ和Bcl xmRNA的表达情况 ;应用TUNEL法检测培养后的细胞凋亡百分率。结果　 ( 1)长期高浓度葡萄糖培养导致大鼠胰岛细胞和小鼠βTc3细胞对葡萄糖刺激的胰岛素分泌反应降低和细胞内胰岛素含量的减少 ;( 2 )高糖培养 14天可以使大鼠胰岛细胞IDX 1和GLUT2mRNA表达明显减少 (P <0 .0 5 ) ,C/EBPβmRNA表达明显增加 ,GKmRNA表达无明显变化 ;( 3 )高糖培养可以明显增加大鼠胰岛细胞和小鼠 βTc3细胞凋亡百分率 ;( 4 )大鼠胰岛细胞高糖培养 14天后Bcl xSmRNA水平明显增加 ,Bcl xLmRNA水平无明显变化 ,Bcl xL/Bcl xSmRNA比率明显减少 (P <0 .0 5 )。结论　 ( 1)长期高糖培养可以诱导大鼠胰岛细胞和小鼠 βTc3细胞凋亡和功能缺陷 ;( 2 )IDX 1表达的变化在大鼠胰岛细胞功能缺陷中起重要作用 ;( 3 )大鼠胰岛细胞的Bcl xL/Bcl xS比率变化在高糖所致的胰岛细胞凋亡中起重要作用。     

调钙素与胰岛素分泌

胰岛素分泌是由很多内源性与外源性动因直接刺激所引起。葡萄糖可能是主要的胰岛素促分泌剂,但氨基酸、胰高糖素与胃肠激素均刺激胰岛 B 细胞释放胰岛素;药物如磺脲化合物以及细胞外液中钾离子浓度的改变亦影响胰岛素释放。这些物质刺激胰岛素分泌的机理还不完全清楚,但有证据表明环磷腺苷(cAMP)与钙离子对胰岛 B 细胞起到连系识别刺激物与胰岛素分泌的信号分子的作用。相当多的证据提示,激素如胰高糖素与胰泌素的作用是由增加细胞内 cAMP 浓度所介     

游离脂肪酸和脂毒性

短期内游离脂肪酸 (FFAs)升高可刺激胰岛素分泌 ,长时间作用可产生抑制效应。FFAs对胰岛 β细胞功能的抑制可能通过改变葡萄糖、FFAs代谢的关键酶的活性或表达 ,使胰岛甘油三酯含量增加 ,β细胞凋亡 ,葡萄糖转运体 2表达下降等多种途径实现。在肥胖和 2型糖尿病中常有FFAs的升高。研究脂毒性与 2型糖尿病发病的关系并指导调治糖尿病的脂代谢异常均有重要意义     

曲格列酮对胰岛β细胞胰岛素分泌的影响及机制研究

研究曲格列酮对胰岛β细胞(MIN6细胞株)胰岛素分泌的影响,并探讨其机制.10μmol/L曲格列酮短期抑制大鼠胰岛和MIN6细胞的葡萄糖刺激的胰岛素分泌(GSIS,P<0.01),增加AMP活化的蛋白激酶(AMPK)、乙酰辅酶A羧化酶(ACC)的磷酸化水平(均P<0.01),而AMPK抑制剂复合物C可使其AMPK、ACC的磷酸化水平以及胰岛素分泌完全恢复.     

围妊娠期胰岛β细胞量动态调控机制的研究进展

妊娠是一种特殊而复杂的生理过程。随着孕周的延长、体重的增加,胎盘产生的胰岛素拮抗激素如催乳素、雌激素、孕激素及皮质激素等逐渐增多,母体会出现对胰岛素的敏感性降低,从而表现出“生理性胰岛素抵抗”。此时,母体胰岛β细胞量通过代偿性扩增,分泌更多的胰岛素来满足机体的需求。     

空腹高血糖对2型糖尿病患者精氨酸刺激试验的影响

目的探讨2型糖尿病(T2DM)血糖水平与胰岛素释放的关系,以了解葡萄糖毒性对胰岛β细胞分泌功能的影响。方法观察146例T2DM患者精氨酸刺激后真胰岛素(TI)、胰岛素原(PI)水平的变化。以胰岛素抵抗(IR)指数作为估测IR的简易参数,并比较T2DM患者在不同FPG状态下,胰岛素分泌减退的检出率的差异。结果(1)T2DM主要表现为IR伴胰岛素分泌不足。(2)比较不同FPG水平T2DM人群中精氨酸刺激后胰岛素分泌减退的检出率:当FPG≥11mmol/L时其检出率明显增加,提示高浓度葡萄糖抑制胰岛素分泌功能的阈值可能在11mmol/L左右。结论葡萄糖毒性作用干扰对β细胞分泌功能的判断,因此,在临床上将T2DM患者的FPG控制在11mmol/L以下进行精氨酸刺激试验,能较为确切地反映其真正的胰岛β细胞功能。     

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.