骨钙素与代谢综合征

代谢综合征(MS)是多种代谢成分异常聚集的病理状态.骨钙素(OC)是成骨细胞合成和分泌的一种非胶原蛋白,越来越多的动物及临床证据表明OC参与了MS的发生和发展.OC能调节脂肪吸收,诱导脂肪细胞分泌脂联素,促进胰岛素释放,减少胰岛素抵抗,且可能参与高血压及动脉粥样硬化性疾病的发生、发展,故对OC的研究将有助于探索MS治疗的新方向.     

新型脂肪因子与动脉粥样硬化性脑梗死关系的研究进展

动脉粥样硬化性脑梗死(ASCI)的多个危险因素涉及代谢综合征(MS)的组分,而脂肪因子作为炎性反应介质在MS及ASCI发生、发展中发挥重要作用。随着研究的不断探索,一些新型脂肪因子逐渐被认识,其可通过参与胰岛素抵抗及炎性反应直接或间接与动脉粥样硬化及ASCI密切相关。充分理解新型脂肪因子在ASCI中的病理生理作用机制,有助于更加合理地将其应用于ASCI的诊治及预防中。     

富含半胱氨酸的酸性分泌蛋白的研究进展

富含半胱氨酸的酸性分泌蛋白(SPARC)主要来源于脂肪组织.血循环中SPARC水平与胰岛素抵抗、肥胖及2型糖尿病( T2DM)有关.胰岛素和瘦素能促进脂肪组织SPARC的分泌.SPARC可能参与了肥胖、T2DM及其并发症的发生、发展,有望成为治疗T2DM及代谢综合征的新靶点.     

Chemerin与代谢综合征发生机制相关

代谢综合征(MS)主要包括中心性肥胖、胰岛素抵抗(IR)、高血压、血脂代谢紊乱等.许多研究表明,脂肪因子失衡在MS病理过程中起着重要作用.Chemerin作为一个重要的生理调节肽,可能参与了肥胖-炎症-MS的病理改变,也可能与IR、内质网应激密切相关.     

RBP4与代谢综合征的研究进展

视黄醇结合蛋白4(RBP4)是新发现的脂肪因子，其通过基因单核苷酸多态性、干扰信号通路、诱导免疫炎症、损伤血管内皮等多种机制参与代谢综合征(MS)相关病理改变的发生与发展。深入研究RBP4与MS相关性及发生机制可为心血管疾病的预防、诊断及治疗提供新思路。     

脂肪性肝病与脂肪组织失调

脂肪性肝病(fattyliver disease,FLD)是遗传-环境-代谢应激相关性疾病,胰岛素抵抗(insuine resistance,IR)作为本病基础机制,介导了与能量稳态失调相关的形态与功能改变,并使其参与表现代谢综合征(metabolic syndrome,MS).脂肪组织(adipose tissue,AT)是全身能量的补给储库,90%以上的总体能量以三酯酰甘油(TG)形式储存于脂肪细胞(adipocyte,AC).AT可通过其TG含量的改变影响能量与脂质失稳态,但更重要的是AC分泌的脂肪细胞因子失常所伴随的多危险因素促使MS发生和演变.肝脏在代谢应激时作为第二能量储库发生肝脂肪储积,脂变肝细胞可出现AC样生物学特性,因此,FLD、IR、AT失调的关联已普遍引起重视[4,5].     

炎症与胰岛素抵抗

胰岛素抵抗(IR)是发生代谢综合征(MS)、2型糖尿病(T2DM)和动脉粥样硬化(AS)的主要病理生理学改变之一，其传统的定义是胰岛素维持正常血糖的能力下降，主要发生在肝、骨骼肌和脂肪组织。虽然从胰岛素基因编码到葡萄糖代谢的过程中的任何步骤出现异常均可发生IR，但对于绝大多数肥胖或T2DM患者，发生IR的分子机制是靶细胞胰岛素受体后信号传导通路的缺陷[Pickup JC，eta1．Diabetes Care，2004，813]。     

瘦素受体基因Gln223 Arg多态性与代谢综合征患者胰岛素抵抗的相关性

目的 研究瘦素受体基因Gln223Arg多态性与代谢综合征(MS)患者胰岛素抵抗的相关性.方法 代谢综合征组167例,对照组216名,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法分析其瘦素受体基因型,并进行临床生化检测.结果 携带A等位基因者发生MS的风险是G等位基因的3.302倍(P<0.01).携带A等位基因的MS患者发生胰岛素抵抗的风险是G等位基因的3.446倍(P<0.01).结论 瘦素受体基因Gln223Arg多态性A等位基因携带者发生MS的风险增加,更容易发生胰岛素抵抗.     

色素上皮细胞衍生因子在代谢综合征中的研究进展

代谢综合征（MS）是代谢层面的心血管危险因子的聚集现象,主要包括高血压、血脂异常、糖尿病、胰岛素抵抗及腹部肥胖等。近年来MS发病率明显上升并严重危害居民的身体健康。色素上皮细胞衍生因子(PEDF)属丝氨酸蛋白酶抑制基因家族,是由多种细胞表达,具有多种生物学活性的分泌性糖蛋白。近年来多项临床试验提示PEDF参与了MS的发生发展,是一个有希望的疾病治疗靶点。本文就PEDF在MS中的作用综述。     

IL-6与代谢综合征

代谢综合征(MS)主要以致动脉粥样硬化的脂代谢紊乱、腹型肥胖、胰岛素抵抗(IR)、高血压、冠心病为特征,其中IR为重要中心环节.八十年代末,发现慢性炎症性疾病可导致外周IR,近年来,众多资料表明,炎症过程参与MS的形成,IL-6作为炎症标志物与MS的发生、发展有着密切联系.本文就近年来IL-6与MS的关系研究进展作一概述.     

Effects of oral contraceptives on glucoregulatory responses to exercise

Some of the effects of oral contraceptives (OCs) to alter glucoregulation may be ameliorated by exercise. To test this premise, the effects of acute aerobic exercise on postprandial glucose, insulin, and C-peptide responses (area under the curve [AUC]) were measured in 8 users of low-dose estrogen and progestin OCs (OC(+)) and 10 women not using OCs (OC(-)). They completed 2 randomly ordered intervention trials: (1) aerobic exercise on 3 consecutive days with a 2.5-hour, 75-g oral glucose tolerance test (OGTT) on day 4, and (2) no exercise for 3 days prior to the OGTT (control trial). The exercise was 50 minutes of treadmill walking at 70% (.-)VO(2max). The groups were similar in age (27 +/- 3 years), waist-to-hip ratio (0.74 +/- 0.01), and cardiorespiratory fitness (32.5 +/- 1.6 mL x kg body mass(-1) x min(-1)). Fasting plasma glucose, C-peptide, and insulin levels were similar (P >.05) between groups in the control trial. In both trials, glucose(AUC) was significantly greater (13%, P <.05) in OC(+). Exercise resulted in a significant (P <.05) decrease in fasting plasma glucose and insulin, insulin(AUC), glucose(AUC) x insulin(AUC), and C-peptide(AUC) in both groups, suggesting enhanced insulin action and/or reduced pancreatic insulin secretion. Hepatic insulin extraction ([C-peptide(AUC) - insulin(AUC)())]/C-peptide(AUC)) was increased following exercise only in OC(+). Thus, insulin action was enhanced in response to exercise in young sedentary women independent of OC use. The mechanisms for the acute exercise effect on insulin action may be different in OC users compared with normally menstruating women.     

Prospective evaluation of insulin resistance and lipid metabolism in women receiving oral contraceptives

OBJECTIVES It has been suggested that normal women receiving oral contraceptives (OC) may develop a series of metabolic side-effects which relate to the risk of cardiovascular disease. These metabolic disturbances include changes in glucose and insulin metabolism, raised serum lipid and lipoprotein concentrations and elevated blood pressure. All these changes indicate that OC might cause insulin resistance. We have prospectively examined the effect of OC on insulin resistance and lipid metabolism including Lp(a) values. PATIENTS The study group comprised 13 normally menstruating Chinese women. DESIGN The study subjects were given a combined triphasic oral contraceptive which was administered on a 21-day on, 7-day off medication cyclic regimen, the first pill being administered on day 5 from the beginning of menses. The metabolic investigations were carried out during luteal phase before OC and again the third week of the third month of OC administration. MEASUREMENTS Metabolic evaluation including insulin secretion and insulin-mediated glucose uptake were evaluated by oral glucose tolerance test and the modification of insulin suppression test. Fasting triglyceride, cholesterol, HDL-cholesterol and Lp(a) concentrations were also measured. RESULTS The plasma glucose and insulin responses during a 75-g oral glucose challenge increased significantly (P<0 05 and P<003, respectively). The steady-state plasma glucose (SSPG) concentrations achieved during constant infusion of glucose, insulin and somatostatin increased significantly after 3 cycles of OC administration (glucose 7–5±08 vs 124±07 mmol/l, P<0001) while the steady-state plasma insulin (SSPI) concentrations were relatively similar (410±14 vs 391 ±7 pmol/l, NS). Plasma triglyceride levels increased significantly (0 81 ±012 vs 1 09±0 19 mmol/l, P<0 03) following OC administration. Fasting plasma cholesterol, HDL cholesterol and calculated LDL cholesterol concentrations did not change as compared with baseline values, nor did the ratio of total cholesterol to HDL cholesterol. The Lp(a) concentrations did not change during the administration of OC (81 ±25 vs 71 ±21 mg/l, NS). CONCLUSIONS These data indicated that intake of OC for 3 cycles induced glucose intolerance, hyperinsulinaemia and insulin resistance in normal menstruating Chinese women. These changes occurred in association with elevated plasma triglyceride concentrations and no alteration in Lp(a) or other lipid values.     

An Old Friend in a New Light: The Role of Osteocalcin in Energy Metabolism

Accumulating evidence suggests interactions between bone and energy metabolism, which may affect the risk of cardiovascular disease. Recent animal studies indicate that osteocalcin (OC) plays a key role in the coordinated regulation of glucose and insulin metabolism while insulin receptors on osteoblasts may regulate bone turnover and circulating OC levels. Association studies, weight loss interventions, and observational data lend some support to the existence and relevance of these mechanisms in humans. However, corroborating evidence from pharmacologic interventions in either bone or glucose metabolism is limited by the number, design, and complex pharmacological effects of the drugs used. Furthermore, such clinical trials are complicated by the alteration of metabolic feedback mechanisms in the insulin resistant state. Purpose‐designed studies are needed to further establish the existence and significance of the role of OC and its subfractions in human insulin metabolism. In this review we summarize existing animal evidence regarding the role of OC and its subfractions in bone and energy metabolism and assess current clinical trial evidence relating to the significance and consequences of this relationship in humans.     

高脂饮食对老年大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响

目的 探讨增龄和高脂饮食对大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响,了解老年大鼠胰岛素抵抗(IR)的发病机制. 方法 将22～24月龄雄性Wistar大鼠随机分为老年对照组和高脂组;4～5月龄大鼠作为青年对照组.老年对照组和青年对照组给予基础饲料,高脂组给予高脂饲料,喂养8周.用高胰岛素-正葡萄糖钳夹实验评价各组大鼠胰岛素敏感性;肝脏三酰甘油经氯仿/甲醇抽提后用全自动生化分析仪测定. 结果 (1)老年对照组空腹血糖、胰岛素和游离脂肪酸均高于青年对照组,高脂组进一步升高,且血清三酰甘油和总胆同醇水平增高;(2)葡萄糖输注率老年对照组[(23.80±2.79)mU·kg-1·min-1]较青年对照组[(30.08±3.89)mU·kg-1·min-1]低,高脂组((18.83±2.18)mU·kg-1·min-1]最低,差异有统计学意义(P<0.01);高脂组8周末较4周末低;(3)肝脏三酰甘油老年对照组较青年对照组升高,分别为(16.6±4.8)μmol/g和(9.6±2.2)μmol/g,高脂组(24.7±6.6)μmol/g较老年对照组进一步升高(P<0.01);在老年组中,肝脏三酰甘油与葡萄糖输注率呈负相关.与空腹血糖呈正相关. 结论 与青年对照组比较,老年对照组更易出现脂肪酸代谢异常及IR;高脂饮食导致老年大鼠肝脏脂质积聚更加严重,进一步加重IR;肝脏脂质堆积可能参与了与增龄和高脂饮食相关IR的发生.     

Osteocalcin and glucose metabolism in postmenopausal women subjected to aerobic training program for 8 weeks

Results of animal studies suggest that osteocalcin (OC) plays an important role in the regulation of carbohydrate metabolism. The aim of the present study was to assess the relationship between biochemical indices of bone turnover and carbohydrate metabolism in postmenopausal women subjected to aerobic training for 8 weeks. The study was conducted on 44 postmenopausal women: 27 of them participated in the training program, and 17 did not undertake any additional physical activity during the study period (control group). Subjects performed a cycle-ergometer physical workout at a level of 70% to 80% of ventilatory threshold intensity for 8 weeks (40-minute sessions, 3 times per week). Serum concentrations of OC, C-terminal telopeptide of type I collagen, osteoprotegerin (OPG), insulin, and glucose were measured; and the homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated before and after the 8-week training program. The training program caused significant decrease in levels of OC (P < .05), HOMA-IR (P < .05), and waist-to-hip ratio (P < .05). No significant changes were observed in C-terminal telopeptide of type I collagen, OPG, insulin, and glucose concentrations. Pretraining OC levels inversely correlated with concentrations of OPG (P < .05), glucose (P < .05), and insulin (P < .05) and with HOMA-IR values (P < .05). Our study revealed an association between serum OC concentrations and metabolic markers in postmenopausal women. Regular physical activity was associated with decrease in central adiposity and OC levels and slight reduction of insulin resistance. However, no direct relationships between training-related changes in OC concentrations and metabolic markers were observed.     

Decreased osteoblast activity in spontaneously diabetic rats

Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused by serum-borne factors. To explore its pathogenesis, we carried out experiments in diabetic and nondiabetic BB rats, using plasma osteocalcin concentrations (OC) as a marker for osteoblast activity. In nondiabetic rats, the iv infusion of glucose (30%, 4 d) did not change OC; sc insulin infusion (4 U/d, 14 d) reduced OC by 27% (p<0.01). In diabetic rats, OC were decreased from the first day of glycosuria (71±5% of paired controls), declining exponentially to 24±3% after 5 wk. Insulin infusion (1,2, and 3 U/d, 14 d) produced gradual restoration of OC. OC were better correlated with insulin-like growth factor-I (IGF-I) than with insulin levels in these experiments. OC were dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73±8 vs 22±4 μg/L before ADX;p<0.001), but not if corticosterone was administered. Ligand blotting of IGF binding proteins showed a marked decrease in two bands (44–49 and 32–35 kDa) 10–14 d after diabetes onset; the density of these bands was increased, but not normalized after ADX. Thus, decreased osteoblast activity is present from the onset of diabetes, is dependent on endogenous corticosterone, and cannot be reproduced by hyperglycemia in nondiabetic rats.     

Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral contraceptive users

This study investigated whether adiponectin, bone formation (osteocalcin) and bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood samples, body composition and aerobic capacity measurements were taken during the follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin, insulin, glucose, insulin resistance, body composition and aerobic capacity did not fluctuate significantly during menstrual cycle in both groups. Osteocalcin and ICTP were lower (p<0.05) in OC compared with NOC, but did not change significantly across menstrual cycle phases in both groups. Estradiol and progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147; p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413), glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin was not affected by menstrual cycle phase and OC use in female rowers, while bone metabolism markers were lower in OC compared to NOC groups. Adiponectin and osteocalcin were interrelated and may characterise energy homeostasis in female athletes.     

Increase in plasma pollutant levels in response to weight loss is associated with the reduction of fasting insulin levels in men but not in women

Environmental pollutants can act as endocrine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with those in plasma insulin levels. Fasting insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 15-week weight loss program induced by a caloric restriction in a sample of obese men and women. Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, P <.05). Fasting insulin and AUC of insulin significantly decreased in men and women after the treatment. In response to weight loss, a significant increase in OC was observed in both genders, and this effect was more pronounced in men. The greater the increase in plasma OC levels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was observed between changes in plasma OC levels and changes in AUC of insulin (-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in response to weight loss remained significantly correlated after correction for fat mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results suggest that weight loss-induced increase in plasma pollutant levels tends to be independently associated with the reduction of fasting insulin levels in men, but not in women. Further studies are needed to verify whether these findings are causally related.     

Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives

Oral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and beta-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P < 0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).