吡格列酮对2型糖尿病患者血清视黄醇结合蛋白4和网膜素1的影响

目的 观察吡格列酮对2型糖尿病患者血清视黄醇结合蛋白4(RBP4)和网膜素1的影响.方法 选择80例新诊断2型糖尿病患者,随机分为对照组和吡格列酮组,每组40例,治疗3个月.比较两组患者治疗前后空腹血糖(FPG)、胰岛素抵抗指数(HOMA-IR)及血清BBP4和网膜素1的水平变化.结果 与对照组比较,吡格列酮组治疗后FPG和HOMA-IR明显降低(P＜0.05),血清RBP4水平也明显降低(P＜0.01),而网膜素1水平明显升高(P＜0.01).Pearson相关分析显示,RBP4与FPG、体质指数及HOMA-IR呈正相关,与低密度脂蛋白呈负相关(P＜0.05);网膜素1与低密度脂蛋白呈正相关,与FPG、体质指数及HOMA-IR呈负相关(P＜0.05).结论 吡格列酮可能通过调节血清RBP4和网膜素1水平而改善胰岛素抵抗.     

High plasma retinol binding protein-4 and low plasma adiponectin concentrations are associated with severity of glucose intolerance in women with previous gestational diabetes mellitus

CONTEXT: Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. OBJECTIVE: We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). RESULTS: Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. CONCLUSIONS: The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.     

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.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

探讨中国汉族人群血清视黄醇结合蛋白4(RBP4)水平与妊娠糖尿病的关系.收集2005年7月至2007年12月在瑞金医院妇产科行常规产前检查的孕妇195例(妊娠糖尿病组99例,正常糖耐量组96例),同时收集65例非妊娠期健康育龄期妇女作为对照组,所有受试者均排除急慢性疾病,并统一用酶联免疫法检测血清RBP4水平.与非妊娠正常对照组相比,妊娠期妇女血清RBP4水平均明显升高,妊娠糖尿病患者血清RBP4水平较正常妊娠妇女显著升高[(43.04±1.85对33.84±2.17)ms/L,P<0.01].在妊娠期妇女中,多元逐步回归分析显示,胰岛素抵抗指数(HOMA-IR)和甘油三酯是血清RBP4水平升高的独市危险因素(r2=0.165).本研究结果提示,妊娠期妇女血清RBP4水平较非妊娠妇女显著升高,而与正常孕妇相比,妊娠糖尿病患者血清RBP4水平更高;在妊娠期妇女中胰岛素抵抗和甘油三酯水平与RBP4水平显著正相关.     

Retinol-binding protein 4 and insulin resistance in preeclampsia

Preeclampsia is characterized by the onset of high blood pressure and proteinuria during pregnancy, which results in substantial maternal and neonatal morbidity and mortality. Insulin resistance has been observed before the onset of preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, has been shown to be a potential regulator of insulin resistance originating from adipose tissue. Here we measured insulin resistance and RBP-4 levels in patients with preeclampsia and in women with normal pregnancies matched for gestational age and body mass index at Okayama University Hospital. Our aim was to examine the potential role of RBP4 in the pathophysiology of this disorder. There were no significant differences in RBP4 levels between all patients with preeclampsia and controls. However, the RBP4 level and homeostasis model assessment as an index of insulin resistance (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly higher than in overweight controls carrying normal pregnancies and in normal weight women with late-onset preeclampsia. In contrast, there were no significant differences between the overweight and normal weight groups among patients with early-onset preeclampsia and in healthy pregnant women. These data suggest that RBP4 might act in the pathophysiology of late-onset preeclampsia via increased insulin resistance in obese women.     

视黄醇结合蛋白4与糖尿病大血管病变的关系及吡格列酮的干预作用

目的研究视黄醇结合蛋白4(RBP4)、单核细胞趋化蛋白-1(MCP-1)在糖尿病动脉粥样硬化大鼠血清中的表达及吡格列酮的干预作用。方法 75只Wistar大鼠随机选取60只以高脂、高糖及链脲佐菌素诱导制成糖尿病模型,造模成功56只大鼠随机分为糖尿病组(38只)和药物干预组(干预组,18只,吡格列酮20 mg·kg~(-1)·d~(-1)灌胃)。另15只大鼠以普通饲料喂养作为对照组。3组大鼠16周后处死,取主动脉全段行HE染色,根据动脉粥样硬化的严重程度,将糖尿病组分为单纯糖尿病组(单纯组,14只)和糖尿病合并动脉粥样硬化组(合并组,24只),测空腹血糖(FBG)、空腹胰岛素(FINS)、TC、TG、HDL-C、LDL-C及血清RBP4,MCP-1,计算动脉粥样硬化指数(AIP)及胰岛素抵抗指数(HOMA-IR)。结果糖尿病组TG、LDL-C、FBG、FINS、RBP4、MCP-1、HOMA-IR、AIP高于对照组(P<0.05),干预组除RBP4与单纯组无差异外,上述指标均较单纯组和合并组下降;RBP4与TG、LDL-C、HOMA-IR、AIP、MCP-1呈正相关,与HDL-C呈负相关。RBP4、TG是糖尿病发生大血管病变的独立危险因素。结论 RBP4是糖尿病发生大血管病变的独立危险因素;吡格列酮对糖尿病大血管病变有保护作用。     

RBP-to-retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes

Aim:  It was recently reported that serum retinol-binding protein (RBP), also known as retinol-binding protein 4 (RBP4), was positively associated with systemic insulin resistance. We hypothesized that an imbalance between RBP and retinol might be the underlying cause for this association.
Methods:  We studied the ratio between RBP and retinol in 233 humans divided into groups depending on normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes (T2DM) and presence or absence of obesity.
Results:  Plasma RBP and retinol levels were lower in patients with T2DM than in individuals with NGT (p < 0.05 and p < 0.0001 respectively). In contrast, RBP-to-retinol ratio was higher in individuals with T2DM (p < 0.0001) and IGT (p < 0.05). Following multivariate adjustment, RBP and retinol correlated positively with low-density lipoprotein (LDL) and triglycerides (p < 0.0001, except retinol and LDL: p < 0.001). RBP-to-retinol ratio correlated positively with glucose 2 h after an oral glucose tolerance test (p < 0.0001) and with C-reactive protein (p < 0.001). Retinol, RBP and adipose tissue RBP messenger RNA (mRNA) levels shared an inverse relationship with plasma interleukin-6, and adipose tissue RBP mRNA levels correlated positively with plasma tumour necrosis factor-α (TNF-α) and skeletal muscle TNF-α mRNA levels.
Conclusions:  Our results suggest that the excess of RBP relative to retinol, assessed as the RBP-to-retinol ratio, is more indicative of T2DM than RBP itself. Hence, the previously reported insulin resistance in mice induced by overexpression or injection of RBP could be because of higher levels of RBP relative to retinol rather than higher total levels of RBP. Moreover, TNF-α may have a role in RBP-mediated adipose to muscle crosstalk.     

Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects

Aims/hypothesis Levels of retinol binding protein (RBP4) are increased in the serum of insulin-resistant human subjects even before overt diabetes develops. RBP4 levels correlate with insulin resistance, BMI, WHR, dyslipidaemia and hypertension. Improvement of insulin sensitivity with exercise training is associated with reduction in serum RBP4 levels. Therefore serum RBP4 may be useful for early diagnosis of insulin resistance and for monitoring improvements in insulin sensitivity. We sought to determine the performance of assays for this application. Subjects and methods We compared quantitative western blotting and three commercially available multiwell immunoassays in parallel measurements of RBP4 concentrations in serum from insulin-sensitive subjects and from insulin-resistant subjects with impaired glucose tolerance or type 2 diabetes. Results The assays yielded different absolute values and magnitudes of elevation of serum RBP4. Western blotting and a sandwich ELISA reported RBP4 concentrations that highly inversely correlated with insulin sensitivity measured by euglycaemic–hyperinsulinaemic clamp. However, western blotting yielded concentrations with a greater dynamic range and less overlap between control and insulin-resistant subjects. Two competitive enzyme-linked immunoassays undervalued serum RBP4 concentrations in insulin-resistant subjects, possibly due to assay saturation. Poor linearity of dilution also limited assay utility. All assays tested exhibited greater immunoreactivity with urinary (C-terminal proteolysed) RBP4 than with full-length RBP4, the predominant form in serum. Conclusions/interpretations These findings support the use of quantitative western blotting standardised to full-length RBP4 protein as a ‘gold standard’ method for measuring serum RBP4 in insulin-resistant states. Other assays should use full-length RBP4 and be extensively cross-validated using other methods.     

Decreased retinol transport proteins in Thai post-menopausal women with osteoporosis

High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 microg/ml, respectively, p = 0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r = 0.172, p = 0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.     

视黄醇结合蛋白4、核因子κB的表达与糖尿病大鼠动脉粥样硬化的相关性

目的探讨视黄醇结合蛋白4（RBP4）、主动脉壁核因子κB（NF-κB）与糖尿病大血管病变的关系。方法Wistar大鼠分为：对照组（NC组）、单纯糖尿病组（（DM组）、糖尿病合并动脉粥样硬化组（DM＋AS组）。测大鼠主动脉NF-κB活性、血清和附睾RBP4水平、FBG、FIns、TG、HDL-C、LDL-C、尾动脉SBP,计算血浆致动脉粥样硬化指数（AIP）及胰岛素抵抗指数（HOMAIR）。结果DM组和DM＋AS组的RBP4、NF-κB、TG、LDL-C、FBG、FIns、SBP、AIP、HOMA-IR高于NC组;DM＋AS组上述指标高于DM组;RBP4与TG、LDL-C、HOMA-IR、AIP、NF-κB、SBP、体脂比成正相关,与HDL-C成负相关。RBP4、TG是糖尿病大血管病变发生的独立危险因素。结论NF-κB与RBP4与糖尿病大血管病变发生相关,RBP4可能通过胰岛素抵抗、炎症机制及脂代谢紊乱参与糖尿病大血管病变的发生。     

Elevated serum retinol-binding protein 4 is associated with insulin resistance in older women

Retinol-binding protein 4 (RBP4), a molecule secreted from adipocytes and hepatocytes, may contribute to insulin resistance and is a potential predictor for type 2 diabetes mellitus. We investigated the association between serum RBP4 concentrations and insulin resistance in perimenopausal women. In addition, we examined associations of serum RBP4 concentrations with age, risk factors of cardiovascular disease, and metabolic syndrome. A total of 73 healthy women were included in this study. Subjects' anthropometric measurements were taken, and body mass index and waist-hip ratio were calculated. Fasting glucose, fasting insulin, serum RBP4, and lipid parameters were examined. These various parameters were compared in subjects younger than and older than 50 years. Serum RBP4 concentrations in women at least 50 years of age were significantly higher than those in women younger than 50 years. In all subjects, serum RBP4 concentrations positively correlated with age, diastolic blood pressure, fasting glucose, and homeostatic assessment model of insulin resistance. After subgroup analysis, serum RBP4 concentrations positively correlated with age, fasting glucose, and homeostatic assessment model of insulin resistance in women at least 50 years of age. In women younger than 50 years, serum RBP4 concentrations positively correlated only with fasting glucose. Serum RBP4 appears to identify age-induced insulin resistance by physiologic changes due to aging or menopause and by increasing hepatic glucose production. However, the clinical implication of RBP4 for detecting cardiovascular disease and metabolic syndrome is not clear.     

Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents

Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.     

Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

Objective  To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).
Design/patients/measurements  We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles.
Results  Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH.
Conclusion  An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.     

Retinol binding protein 4, low birth weight-related insulin resistance and hormonal contraception

It has been recently reported that increased serum levels of retinol binding protein 4 (RBP4), a molecule secreted by adipocytes and liver, could be an early marker of insulin resistance (IR). We determined whether serum RBP4 was increased in low birth weight (LBW)-young women as a model of early-onset IR, through a historical prospective study. The study-population included 35 LBW and 35 born at term appropriate for gestational age (term AGA) young women. Metabolic evaluations included the composite-insulin sensitivity index (composite ISI). Serum RBP4 was measured with a competitive enzyme-linked immunosorbent assay (ELISA). RBP4 levels were similar in LBW and term AGA women, while composite ISI was significantly lower in the former group. With multivariate logistic regression analysis hormonal contraception (HC) use but not birth weight, diabetes in either parents and body mass index was significantly associated with higher RBP4 levels: odds ratio = 10.6; 95% confidence interval (CI) = 2.4–76.6. In spite of higher RBP4 levels in women under HC, composite ISI was similar in women with or without HC. Women under HC also exhibited significantly higher levels of sex hormone binding globulin (SHBG), triglycerides, cholesterol, and C-reactive protein (CRP), and all of them, but not composite ISI, were significantly correlated with RBP4 levels. In conclusion, RBP4 serum level was not a marker of IR but, for the first time, it is documented a sustained increase of serum RBP4 under HC. Pathophysiological and clinical significance of this novel finding requires further investigations     

检测视黄醇结合蛋白4在非酒精性脂肪性肝病中的意义

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清视黄醇结合蛋白4(RBP4)的临床意义。方法选择NAFLD肝患者62例,正常对照60例,采用ELISA方法测定空腹血清RBP4,同时检测其血糖、血脂、肝功能及胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR)。结果与正常对照组比较,NAFLD患者的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度酯蛋白(LDL-C)、血清胰岛素(FINS)、HOMA-IR、ALT、AST和RBP4显著增高(P<0.01),而且NAFLD患者治疗后血清RBP4水平显著降低。相关分析显示,血清RBP4与FBG、TC、TG、FINS、HOMA-IR呈正相关。结论在NAFLD的发病过程中,RBP4可能参与其发病,在其早期诊断和评判肝脏损害程度中有一定的临床意义。     

Retinol-binding protein 4 is not associated with insulin resistance in pregnancy

Retinol-binding protein 4 (RBP4) is an adipokine proposed to be specifically associated with insulin resistance (IR). We examined whether serum levels of RBP4 were associated with IR in pregnancy. One hundred seventy-two women with gestational diabetes mellitus (GDM) and 361 pregnant Thai women who did not have GDM but had a positive 50-g glucose challenge test result (plasma glucose level was ≥7.2 mmol/L after 1 hour) were enrolled. We measured fasting serum levels of RBP4 and assessed IR at a 100-g oral glucose tolerance test. We found a higher degree of IR in the GDM group compared with the non-GDM group, but serum RBP4 levels between the 2 groups were not different. Retinol-binding protein 4 levels were associated with serum triglyceride levels but were not associated with the degree of IR assessed by homeostasis model assessment or quantitative insulin sensitivity check index. Our results suggest that serum RBP4 levels in pregnancy are not associated with IR.     

Retinol-binding protein 4 levels are elevated in polycystic ovary syndrome women with obesity and impaired glucose metabolism

OBJECTIVE: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4), a new fat-derived adipokine, has been described to be elevated in obesity and type 2 diabetes. The aim of the present study was to investigate whether serum RBP4 levels are correlated with metabolic parameters, indices of insulin resistance, and endocrine variables in German PCOS women. DESIGN: We assessed the correlation between metabolic and endocrine parameters with RBP4 levels in 200 PCOS patients and 64 healthy controls. METHODS: Serum RBP4 was measured by enzyme-linked immunosorbent assay (Immundiagnostik AG, Bensheim, Germany). In addition, anthropometric variables, clinical signs of hyperandrogenism, and body fat were evaluated, and a glucose tolerance test was performed to assess parameters of insulin resistance and glucose metabolism. RESULTS: Taking the entire PCOS cohort, RBP4 levels were positively correlated with body mass index (BMI), body fat, waist circumference, fasting glucose, and area under the curve for glucose (all P<0.05), but not with indices of insulin resistance. On the other hand, PCOS women with impaired glucose metabolism had higher RBP4 levels than PCOS women with normal glucose metabolism (median 30.6, range 23.3-73.9 versus median 26.3, range 6.4-61.4, P<0.05). Furthermore, no differences were found in RBP4 levels between lean PCOS women and BMI-matched healthy controls. CONCLUSION: In German PCOS women, serum RBP4 levels are associated with obesity and parameters of glucose metabolism but not with PCOS per se.     

桂皮醛抗糖尿病作用及其分子机制

目的 观察桂皮醛抗糖尿病的效果并探讨其药理机制.方法 将清洁级雄性Wistar大鼠40只分为正常对照组(8只,普通饮食),其余32只大鼠予高脂高糖饮食、链脲佐菌素,造成2型糖尿病成模大鼠(24只),分为糖尿病对照组、二甲双胍治疗组(200 mg·kg-1·d-1)和桂皮醛治疗组(40 mg·kg-1·d-1),每组8只.经药物干预4周后测各组体质量、空腹血糖、血脂、空腹血胰岛素并计算胰岛素抵抗指数(HOMA-IR),采用Western blot对血清及组织的视黄醇结合蛋白4(RBP4)、葡萄糖转运载体4(GLUT4)蛋白水平进行分析,免疫组织化学染色分析组织p85α和胰岛素受体底物1(IRSI)蛋白表达水平.结果 与糖尿病对照组比较,桂皮醛降糖、降脂、提高胰岛素敏感性效果明显[空腹血糖:(22.7±4.0)比(7.5±1.5)mmol/L;甘油三酯:(1.53±0.13)比(0.77±0.15)mmol/L;HOMA-IR:8.0±3.0比61.2±12.1,P<0.01];糖尿病组血清RBP4升高了1.68倍,GLUT4蛋白水平与正常对照组比较下调了33%～44%,差异有统计学意义(P<0.05);与糖尿病组比较,桂皮醛明显降低了(28.6%)血清RBP4水平(P<0.05),下调肌肉p85a蛋白表达(0.51±0.05比0.43±0.04,P<0.05),同时上调IRSl蛋白表达(0.52±0.05比0.03±0.06,P<0.05),肝脏、肌肉和脂肪组织的GLUT4蛋白表达升高.结论 桂皮醛具有良好的降糖调脂、提高胰岛素敏感性的效果,其药理机制与降低血清RBP4水平以及调节肌肉组织p85α和IRSI蛋白表达有关.     

Proinsulin in pregnant women with normal glucose tolerance or mild gestational diabetes mellitus.

Pregnancy is characterized by peripheral insulin resistance, which is physiologically compensated by an increase in insulin secretion. Type 2 diabetes and impaired glucose tolerance (IGT) have been associated with an inappropriate increase in insulin precursors, namely proinsulin. The aim of this study was to determine levels of proinsulin (PI), specific insulin (SI) and the proinsulin-to-specific insulin (PI/SI) ratio in consecutive pregnant women (n = 209) with normal glucose tolerance (NGT), as assessed by a 2h oral glucose tolerance test, and with mild gestational diabetes (GDM), in comparison to 32 healthy, non-pregnant women. Furthermore, we related these variables to surrogate markers of insulin resistance and insulin secretion. We found no significant differences in the levels of PI and the PI/ SI ratio between pregnant and non-pregnant women (PI: 5.0 +/- 3.6 vs. 4.8 +/- 3.5 pmol/L, p = NS), and between pregnant women with mild GDM and NGT (PI: 5.4 +/- 2.4 vs. 4.9 +/- 3.9 pmol/L, p = NS). SI was elevated in women with mild GDM (112.2 +/- 47.3 vs. 94.8 +/- 43.0 pmol/L in NGT, p=0.02). PI was related to fasting glucose (r = 0.17, p < 0.02), but not post-load glucose levels, and to fasting insulin [specific insulin: r = 0.67, p = 0.0001; total immunoreactive insulin (IRI): r = 0.69, p = 0.0001], as well as post-load insulin levels (IRI at 120 min: r = 0.18, p < 0.03). The PI/SI ratio showed no association with fasting or post-load glucose or insulin levels. Pregnant women presented with a metabolic pattern suggestive of enhanced insulin resistance, namely increased fasting and post-load insulin levels. In women with mild GDM, fasting and post-load hyperglycemia, as well as an additional increase in insulin resistance was found. Group differences weakened when accounting for differences in body weight. The data of the present study suggest that in normal pregnancy as well as mild GDM metabolic alterations including enhanced insulin resistance and hyperglycemia do not result in an increase in circulating levels of proinsulin, both in absolute terms and relative to levels of specific insulin, as indicated by the proinsulin-to-specific insulin ratio.     

Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss

CONTEXT: There are limited and controversial data concerning the relationships between retinol-binding protein 4 (RBP4), weight status, and insulin resistance in obese humans and especially in children. OBJECTIVE: Our objective was to study the longitudinal relationships among RBP4, insulin resistance and weight status in obese children. DESIGN, SETTING, AND PATIENTS: We conducted a 1-yr longitudinal follow-up study in a primary-care setting with 43 obese children (median age 10.8 yr) and 19 lean children of same the age and gender. INTERVENTION: Our outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy. MAIN OUTCOMES MEASURES: Changes of weight status (body mass index sd score), RBP4, molar RBP4/serum retinol (SR) ratio, insulin resistance index homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). RESULTS: Obese children had significantly (P < 0.01) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children. In multiple linear regression analyses adjusted to age, gender, and pubertal stage, RBP4 was significantly correlated to insulin and body mass index. Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index, insulin, and RBP4 concentrations compared with prepubertal children. Changes of RBP4 correlated significantly to changes of insulin (r = 0.29), HOMA index (r = 0.29), QUICKI (r = 0.22), and weight status (r = 0.31). Substantial weight loss in 25 children led to a significant (P < 0.001) decrease of RBP4, RBP4/SR, blood pressure, triglycerides, insulin, and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss. CONCLUSION: RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses, suggesting a relationship between RBP4, obesity, and insulin resistance in children.