The association between the triglyceride to high-density lipoprotein cholesterol ratio with insulin resistance (HOMA-IR) in the general Korean population: based on the National Health and Nutrition Examination Survey in 2007-2009

Aim

To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction.

Methods

Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods.

Result

Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71 ± 0.93 ng/ml versus 2.69 ± 2.02 ng/ml, p = 0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452 ± 0.254 ng/ml versus 0.409 ± 0.275 ng/ml, p > 0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR) = 1.71, 95% confidence interval (1.30-2.25); p < 0.0001].

Conclusion

The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group.     

糖皮质激素诱导胰岛素抵抗的分子机制

糖皮质激素是体内重要的胰岛素拮抗激素,可诱导胰岛素抵抗。糖皮质激素可以干扰骨骼肌细胞的葡萄糖摄取和利用,抑制脂肪组织中葡萄糖转运蛋白（GLUT）-4的胞内分布及糖转运活性从而抑制糖摄取。并可通过调节脂肪细胞因子如脂联素、抵抗素、瘦素、内脏脂肪素的分泌,影响胰岛素的敏感性。此外,糖皮质激素还可抑制胰岛β细胞功能,使胰岛素分泌减少,并触发胰岛细胞凋亡。     

新诊断2型糖尿病患者血浆内脂素水平变化研究

目的探讨新诊断2型糖尿病(T2DM)患者血浆内脂素水平变化。方法检测113例新诊断T2DM患者和102例正常对照的空腹血浆内脂素水平和相关临床指标。结果新诊断T2DM患者血浆内脂素水平高于正常对照组(P0.05)。多重线性回归分析显示腰臀比和空腹血糖是影响血浆内脂素水平的独立相关因素。结论血浆内脂素水平变化与糖代谢密切相关,它可能在T2DM的发病机制中起着一定作用。     

Effect of adiponectin on ATDC5 proliferation,differentiation and signaling pathways

Adiponectin, an adipose-secreted adipocytokine, exhibits various metabolic functions but has no known effect on bone development through the growth plate and specifically, in chondrocytes. Using the mouse ATDC5 cell line, a widely used in vitro model of chondrogenesis, we demonstrated the expression of adiponectin and its receptors during chondrogenic differentiation. Adiponectin at 0.5 μg/ml increased chondrocyte proliferation, proteoglycan synthesis and matrix mineralization, as reflected by upregulation of the expression of type II collagen, aggrecan, Runx2 and type X collagen, and of alkaline phosphatase activity. Quantitative RT-PCR and gelatin zymography showed a significant increase in the matrix metalloproteinase MMP9's expression and activity following adiponectin treatment. We therefore concluded that adiponectin can directly stimulate chondrocyte proliferation and differentiation. To evaluate the underlying mechanisms, we examined the effect of adiponectin on the expression of chondrogenic signaling molecules: Ihh, PTHrP, Ptc1, FGF18, BMP7, IGF1 and p21 were all upregulated while FGF9 was downregulated. This study reveals novel and direct activity of adiponectin in chondrocytes, suggesting its positive effects on bone development.     

多囊卵巢综合征患者血清脂肪细胞因子与胰岛素抵抗的相关性研究

目的 探讨PCOS患者血清脂肪细胞因子与胰岛素敏感性的相关性.方法 将PCOS患者60例分为肥胖组PCOS36例、非肥胖组PCOS24例,将同期就诊的男方因素不孕症患者(正常体重)26例作对照组.进行内分泌代谢指标测定,采用空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)评估胰岛素敏感性;并应用酶联免疫吸附法测定血清游离脂肪酸(FFA)、瘦素及C反应蛋白(CRP),放射免疫法测定血清脂联素(APN)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6.结果 (1)肥胖组PCOS的血清APN为(10±7)mg/L,低于非肥胖组PCOSE(17±9)mg/L]和对照组,均P＜0.01;FFA为(548±105)μmol/L,高于非肥胖组PCOS[(427±67)μmoL/L]和对照组,P＜0.01;血清瘦素水平为(42±21)μg/L,高于非肥胖组PCOS[(24±13)μg/L]和对照组,均P＜0.01.非肥胖组PCOS与对照组间APN、FFA和瘦素差异无统计学意义.血清IL-6肥胖组PCOS[(173 4-184)ng/L]和非肥胖组PCOS[(184±44)ng/L]均高于对照组(P＜0.05、P＜0.01);血清TNF-α非肥胖组PCOS[(0.97±0.33)μg/L]和肥胖组PCOS[(0.82 4-0.21)μg/L]均高于对照组(P＜0.01,P＜0.05);非肥胖组PCOS TNF-α高于肥胖组(P＜0.05).非肥胖组和肥胖组的PCOS患者血清中CRP高于对照组,但差异无统计学意义(P＞0.05).(2)瘦素与人体质量指数(BMI)、腰臀比及HOMA-IR呈正相关(P＜0.01),APN与BMI、腰臀比及HOMA-IR呈负相关(P＜0.01).(3)BMI和TNF-α是FINS的独立影响因素,APN是除FINS、空腹血葡萄糖、BMI外,对HOMA-IR的独立影响因素.结论 炎性因子可能参与了非肥胖型PCOS患者IR的发生;而肥胖型PCOS IR的进一步加重可能与其脂肪组织分泌瘦素、FFA增多及分泌APN减少相关.     

脂联素在重症急性胰腺炎脂肪组织中的表达及意义

目的探讨脂联素在重症急性胰腺炎(severe acute pancreatitis,SAP)脂肪组织中的表达、作用及意义。方法通过牛磺胆酸钠诱导建立大鼠SAP模型,12只SD大鼠随机分成2组:假手术对照组(N组)、SAP组;分别于24 h内处死,取附睾旁脂肪组织,采用RT-PCR行mRNA表达量检测,HE染色观察脂肪组织炎症改变情况。结果与N组相比,SAP组炎症因子IL-10、TNF-αmRNA表达上升(P0.05),而TGF-β1及脂联素的表达明显下降(P0.01)。结论脂联素在SAP中起保护性作用,有可能成为预测SAP严重程度及判断预后的指标。     

脂肪细胞因子CTRP4转基因鼠的构建与鉴定

目的建立人CTRP4基因的转基因小鼠,为脂肪细胞因子CTRP4的体内功能研究奠定基础。方法首先构建人CTRP4的转基因小鼠线性化表达载体,再利用显微注射的方法将载体注射入小鼠受精卵,从而构建人CTRP4的首建鼠(Founder)并与野生型小鼠交配繁殖得到F1代阳性小鼠,再通过近亲繁殖与测交的方法,得到CTRP4转基因纯合子小鼠,并通过PCR和western blot的方法对纯合子小鼠进行鉴定。结果得到人CTRP4转基因小鼠纯合子小鼠两个品系,western blot鉴定该转基因小鼠心脏,肝脏,脑,肾脏等多种组织中均呈现CTRP4高表达。结论成功构建了人CTRP4转基因小鼠纯合子小鼠。     

肥胖与急性肺损伤研究进展

2009年的H1N1爆发,流行病学研究发现肥胖为H1N1病毒感染高死亡率的独立危险因素.由于肥胖可引起生理生化改变,可能更易并发急性肺损伤;肥胖能引起急性肺损伤患者炎症、内皮功能损害和氧应激等变化.现就肥胖与急性肺损伤的发病机制作一综述.     

慢性应激诱导DPP-4表达及对脂肪炎症和代谢的影响

目的　分析慢性应激诱导脂肪二肽基肽酶-4（DPP-4）表达及对脂肪炎症和糖代谢的影响。 方法　雄性SPF级小鼠20只随机分慢性应激（Stress）组和正常对照（Control）组。Stress组小鼠每天在自制式束缚器中限制活动2 h，实验持续14 d。采用免疫组化方法检测巨噬细胞表面标志物（CD11b）在脂肪中的表达，实时定量PCR法检测脂肪组织中DPP-4、细胞因子（Adiponectin、MCP-1、IL-6、TNF-α）及糖代谢（IRS-1、GLUT-4）等指标的mRNA的相对表达量；ELISA法检测DPP-4酶活性及GLP-1浓度。 结果　Stress小鼠腹部白色脂肪组织（WAT）与Control组相比显著的退缩及其重量显著降低（P<0.001）。Stress组WAT出现大量的单核细胞、中性粒细胞浸润反应和炎症性改变；Stress显著降低Adiponectin的表达，并显著增高MCP-1、IL-6、TNF-α的mRNA表达及其血液中的浓度（P<0.001）；Stress组WAT组织中DPP-4 mRNA表达及其血液中的活性显著增高，而GLP-1血液中的浓度显著降低（P<0.001）；Stress组WAT组织中IRS-1及GLUT-4的mRNA水平显著低于Control组（P<0.001）。 结论　慢性应激诱导脂肪DPP-4异常表达，进而引起脂肪炎症和糖代谢异常等反应。     

Adipocytokines and breast cancer

A substantial number of studies have revealed that a growing list of cancers might be influenced by obesity. In this regard, one of the most prominent and well-characterized cancers is breast cancer, the leading cause of cancer death among women. Obesity is associated with an increased risk for the occurrence and development of breast cancer particular in postmenopausal women. Moreover, the relationship between adiposity and breast cancer risk is complex, with associations that differ depending on when body size is assessed (eg, premenopausal vs postmenopausal obesity) and when breast cancer is diagnosed (ie, premenopausal vs postmenopausal disease). Obesity is mainly due to excessive fat accumulation in the regional tissue. Adipocytes in obese individuals produce endocrine, inflammatory, and angiogenic factors to affect adjacent breast cancer cells. Adipocytokines, are biologically active polypeptides that are produced either exclusively or substantially by adipocytes, play a critical and complex role, and act by endocrine, paracrine, and autocrine pathways in the malignant progression of breast cancer. Furthermore, the increased levels of leptin, resistin, and decreased adiponectin secretion are directly associated with breast cancer development. And there are also many studies indicating that adipocytokines could mediate the survival, growth, invasion, and metastasis of breast cancer cells by different cellular and molecular mechanisms to reduce the survival time and prompt the malignancy. In present review, we discuss the correlations between several adipocytokines and breast cancer cells in obesity as well as the underlying signaling pathways to provide the novel ideas for the prevention and treatment of breast cancer.