高血压家族遗传因素、超重与胰岛素抵抗的关系及其相加作用的研究

为探讨高血压家族遗传因素、超重与胰岛素抵抗（ＩＲ）关系及其相加作用，本研究采用家系调查法，对比分析高血压家系直系亲属正常血压者和对照家系直系亲属的有关参数。两家系均按超重和非超重（ＢＭＩ≥２５ｋｇ／ｍ２或ＢＭＩ＜２５ｋｇ／ｍ２）分组。结果表明：四组间除血糖外，胰岛素及其对数转换值、胰岛素敏感指数均有显著的统计学差异；高血压家系非超重组胰岛素敏感指数显著低于对照家系相应组，调整年龄、性别后，各组间胰岛素水平呈高血压家系超重组＞对照家系超重组＞高血压家系非超重组＞对照家系非超重组，而且，无论高血压或对照家系，超重组胰岛素均显著高于非超重组，高血压家系超重组与其它各组间差异均达到统计学显著性水平。这些结果提示，有家族遗传因素者在高血压发生前就可能存在ＩＲ，且遗传因素和超重对ＩＲ具有相加作用。     

替米沙坦对肥胖性高血压患者体脂、血脂及胰岛素抵抗的影响

目的探讨替米沙坦对肥胖性高血压患者体脂、血脂、胰岛素抵抗的影响。方法 BMI≥25 kg/m2的原发性高血压患者60例,随机分成观察组和对照组,并分别给予替米沙坦和硝苯地平缓释片干预,观察干预前后BP、BMI、腰臀比（W/H）、TC、LDL-C、TG、胰岛素抵抗指数（IRI）、高敏C反应蛋白（hsCRP）等指标变化。结果与干预前比较,干预后12、24周两组BP均下降（P〈0.01）,干预后24周观察组W/H、TGI、RI、hsCRP下降（P〈0.01或P〈0.05）。观察组IRI、hsCRP的变化与SBP、DBP、BMI、W/H、TG等呈直线相关。结论替米沙坦除良好的降压外,有一定的减轻腹型肥胖、控制TG和改善胰岛素抵抗的作用。     

Association of three insulin resistance indices with hypertension and body weight among Uyghur adults in rural areas of Xinjiang,China

Obesity and insulin resistance are significant contributors to hypertension. There is a high prevalence of obesity among Uyghurs in the rural areas of Xinjiang, China. Therefore, this study aimed to explore the association between insulin resistance indices and hypertension according to different body weights in rural Uyghur residents of Xinjiang, China. A total of 12 813 local Uyghur residents were recruited for the study. Excluding those with incomplete data and those using antihypertensive, lipid‐lowering, or glycemic drugs, 9577 permanent residents were eligible for the study. Three insulin resistance indicators were calculated: triglyceride to high‐density lipoprotein cholesterol ratio, product of fasting triglyceride and glucose (TYG), and metabolic score for insulin resistance. Multivariate logistic regression analysis was performed to estimate the association between the three non‐insulin‐based insulin resistance indices and the risk of hypertension for different body weights. TYG was significantly associated with hypertension in the normal‐weight group, particularly in women. In the obese group that was obese, all three indicators were associated with hypertension. Since TYG was associated with hypertension in the groups with normal weight and obesity, it may be useful as a reference indicator for insulin resistance. This indicator may provide a basis for the identification and management of hypertension risk among adults in the Uyghur population.     

Pathophysiological connections between gallstone disease,insulin resistance,and obesity

Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.     

原发性高血压分级与胰岛素抵抗、血浆内皮素-1的关系

目的探讨血浆内皮素-1(endothelin-1,ET-1)、胰岛素抵抗(insulin resistance,IR)和原发性高血压(高血压)分级之间的关系。方法入选150例门诊及体检科新发现的高血压患者,按照2010年《中国高血压防治指南》诊断标准和血压分级原则,分为高血压1级组(52例)、高血压2级组(50例)、高血压3级组(48例),分别检测患者的血浆ET-1、空腹血糖(fasting blood glucose,FBG)、空腹血清胰岛素(fasting serum insulin,FINS)浓度。IR检测采用HOMA法,计算胰岛素敏感指数(insulin sensitivity index,ISI)。结果高血压3级组ISI明显小于高血压2级组和高血压1级组,差异有统计学意义(0.31±0.07 vs.0.43±0.06 vs.0.52±0.03,P<0.05);高血压2级组ISI明显小于高血压1级组,差异有统计学意义(P<0.05)。高血压3级组血浆ET-1浓度明显高于高血压2级组和高血压1级组,差异有统计学意义[(166.27±10.58)ng.L-1vs.(156.74±12.11)ng.L-1vs.(148.62±11.45)ng.L-1,P<0.05];高血压2级组血浆ET-1浓度明显高于高血压1级组,差异有统计学意义(P<0.05)。相关分析结果显示,ISI与收缩压呈负相关(r=-0.58,P<0.05),与舒张压也呈负相关(r=-0.56,P<0.05);ET-1与收缩压呈正相关(r=0.60,P<0.05),与舒张压也呈正相关(r=0.59,P<0.05)。结论 IR及血浆ET-1浓度升高与高血压血压分级有密切关系。     

Relation of depot-specific adipose inflammation to insulin resistance in human obesity

BACKGROUND:

A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity.

OBJECTIVE:

To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat.

METHODS:

We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI⩾30 kg m⁻²) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS⁺ or CLS⁻ based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLS_s), omental (CLS_o) and mesenteric (CLS_m) adipose depots.

RESULTS:

The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS⁺) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS⁺ status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved.

CONCLUSIONS:

In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.     

肥胖相关性肾病患者胰岛素抵抗状态评估指标的分析

目的:以胰岛素抵抗指数(HOMA-IR)作为标准评价肥胖相关性肾病(ORG)患者胰岛素抵抗(IR)状态,并探讨血脂评估ORG患者个体IR的价值。方法:选取经临床和肾脏病理证实的ORG患者36例,健康体检的正常人266例作为对照(空腹血糖<6·1mmol/L,且BMI<25kg/m2),测定两组人群的空腹血糖、胰岛素、总胆固醇(Chol)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,计算HOMA-IR以评价ORG患者的IR状态。分析ORG人群的Chol、TG、HDL-C、LDL-C、TG/HDL-C比值与HOMA-IR的相关关系。结果:ORG患者的HOMA-IR平均值为6·32±4·11,显著高于对照组(1·98±0·89,P<0·001)。ORG的Chol、TG、TG/HDL-C比值较对照组显著升高,HDL-C显著降低(P<0·01),LDL-C升高(P<0·05)。其中以TG、TG/HDL-C比值升高更明显。Chol、TG、HDL-C、LDL-C、TG/HDL-C比值与HOMA-IR相关系数分别为0·195、0·122、-0·045、-0·019、0·143,均无统计学差异(P>0·05)。结论:HOMA-IR作为评估IR的指标同样适用于ORG患者。虽然血脂水平也被用于IR的评估,但对于ORG患者并不是理想指标。     

Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients

OBJECTIVE: The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients. METHODS: Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined. RESULTS: Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine. CONCLUSIONS: Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.     

Abdominal obesity and insulin resistance after an episode of acute pancreatitis

BackgroundEmerging evidence indicates that individuals after an episode of acute pancreatitis (AP) are at an increased risk of developing metabolic derangements. While the link between general obesity and insulin resistance (IR) is well established, only a few studies have investigated the association between abdominal obesity and IR. The aim of this study was to investigate the associations between abdominal obesity and several indices of IR in individuals after an episode of AP.MethodsPatients were eligible for this cross-sectional study if they were previously admitted with a primary diagnosis of AP based on the recent international guidelines. Fasting venous bloods were collected to measure glucose, insulin, free fatty acids, glycerol, adiponectin (AD), omentin (OM), and vaspin (VAS). The IR indices – HOMA-IR, Adipo-IR, insulin*glycerol (IG) index, HOMA-AD, HOMA-OM, and HOMA-VAS were calculated. Modified Poisson regression was conducted, with statistical model adjusting for patient-, metabolic-, and pancreatitis-related risk factors. Areas under ROC curve were calculated and Bland–Altman plots were created.ResultsOf the 92 individuals recruited, 41 had abdominal obesity. HOMA-IR, IG index, HOMA-OM, and HOMA-VAS were significantly associated with abdominal obesity, both in unadjusted and adjusted models. Area under ROC curves for HOMA-IR, IG index, HOMA-OM, and HOMA-VAS were 0.698, 0.695, 0.756, and 0.735, respectively. There was a good agreement between observed HOMA-IR values and values obtained from HOMA-OM (P = 0.733) and HOMA-VAS (P = 0.595).ConclusionIndividuals with abdominal obesity after AP have a significantly higher IR, independent of diabetes and other covariates. Visceral adipose tissue specific adipokines, omentin and vaspin, hold promise for future clinical investigation of tissue-specific IR.     

高血压病患者血清总胆红素浓度与胰岛素抵抗水平的关系

目的　探讨高血压病患者血清总胆红素浓度与胰岛素抵抗、血糖、血脂、尿酸 (UA)的关系。方法　测定 16 5例高血压病患者的空腹血清总胆红素、血红蛋白 (Hb)、UA、总胆固醇、甘油三酯 (TG)、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的浓度 ,口服葡萄糖耐量试验和胰岛素释放试验测定血浆葡萄糖浓度和血清胰岛素浓度 ,计算葡萄糖曲线下面积 (AUCG)和胰岛素曲线下面积 (AUCIN) ,稳态模式评估法计算胰岛素抵抗指数 (HOMA IR)。以HOMA IR 5 0 %位点 ,作为判断胰岛素抵抗的切割点 ,将高血压病患者分为胰岛素抵抗 (IR)组与胰岛素敏感 (IS)组。结果　血清总胆红素浓度 ,IR组为 (9.3± 3.3) μmol L显著低于IS组 (12 .0± 3.8) μmol L ,与HOMA IR、腰臀围比、收缩压、Hb、空腹胰岛素、TG、AUCG 、AUCIN呈显著相关关系 ;逐步回归分析显示 ,HOMA IR、AUCG 与Hb为血清总胆红素浓度的独立预测因子 ,血脂和UA均非血清总胆红素浓度的独立预测因子。结论　与胰岛素敏感的高血压病患者相比 ,伴胰岛素抵抗的高血压病患者有较低的血清总胆红素水平 ;高血压病患者血清总胆红素浓度与胰岛素抵抗、血糖与Hb直接相关 ,与血脂、UA无直接相关。     

Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors

Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.     

腹型肥胖的研究进展

近年来腹型肥胖作为代谢综合征最重要的特征得到了广泛关注."脂质异位沉积"学说提出腹部皮下脂肪与内脏脂肪一样,在促进胰岛素抵抗形成的过程中发挥关键作用,同时也是导致心血管代谢风险的重要因素,而并非仪表现为既往所认为的机体保护作用.提示无论腹部皮下脂肪还是内脏脂肪堆积引起的腰围增加都应当得到足够的重视,也进一步支持将腰围作为代谢综合征工作定义中肥胖的诊断标准.腹型肥胖的治疗基础仍是生活方式干预,而体液因子、胃肠道激素及棕色脂肪研究的开展为腹型肥胖提供了新的治疗方向.     

腹型肥胖脑血栓患者阿司匹林抵抗的初步研究

目的探讨腹型肥胖脑血栓患者是否存在阿司匹林抵抗及其原因。方法选择病情稳定的脑血栓患者125例,根据腰围分为腹型肥胖组和非腹型肥胖组,测定两组的血小板聚集率、TNF-a、IL-6和C反应蛋白。Logistic多元回归分析用于评价阿司匹林抵抗和各种危险因素的联系程度。结果腹型肥胖组阿司匹林抵抗的发生率、TNF-a、IL-6和C反应蛋白均明显高于非腹型肥胖组（P〈0．05）,年龄、TNF—a、IL-6和C反应蛋白是脑血栓患者发生阿司匹林抵抗的独立危险因素。结论腹型肥胖脑血栓患者易发生阿司匹林抵抗,可能与患者体内的炎症介质增加有关,临床工作中要高度重视该类患者。     

The use of U‐500 regular insulin in the management of patients with obesity and insulin resistance

The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin. This article reviews the published literature on the properties of U‐500 insulin and its use in clinical practice. U‐500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U‐100 insulin. Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U‐500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control. To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U‐500 insulin who are admitted to hospital.     

胰岛素抵抗、高胰岛素血症与原发性高血压心脏超声心动图改变的关系

目的探讨胰岛素抵抗（IR）、高胰岛素血症（HIS）对原发性高血压（EH）心脏损害在超声心动图改变中的影响。方法60例EH患者进行口服葡萄糖耐量试验（OGTT）同时测定胰岛素、C肽释放,并接受超声心动图检查,其中EH伴HIS患者（HIS组）30例,单纯EH患者（对照组）30例。结果HIS组与对照组比较,OGTT各时相血糖无明显差异（P〉0.05）,但胰岛素、C肽均显著升高（P〈0.01）。HIS组IAI明显小于对照组（P〈0.01）。两组心脏形态学改变及左室质量指数、相对壁厚度比较均有统计学差异（P均〈0.05）。HIS组A峰、A/E较对照组明显增高（P〈0.05）。结论EH伴HIS患者存在IR,IR、HIS参与了左室肥厚的发生和发展,加重了EH患者心脏舒张功能的损害。     

Altered adrenocorticotropin and Cortisol secretion in abdominal obesity: implications for the insulin resistance syndrome

Abstract. Objectives. To investigate the relationship between the pituitary-adrenocortical function, abdominal obesity, and insulin resistance syndrome. Design. A prospective study. Setting. Helsinki University Hospital, Finland. Subjects. Sixty-six healthy males aged 30–55 years. Main outcome measures. Insulin, C-peptide, Cortisol and ACTH responses during the oral glucose tolerance test (OGTT), and the Cortisol response to dexamethasone suppression and intravenous adreno-corticotrophic hormone (ACTH) stimulation. Results. The subjects in the highest tertile of the waist-to-hip ratio (WHR) had lower high-density lipoprotein cholesterol (HDLC) (P < 0.05), but higher triglyceride (TG), insulin, and C-peptide levels, ACTH response to glucose at 2 h, and Cortisol response to ACTH (P < 0.01) than those in the lowest tertile. The Cortisol response to ACTH correlated positively, but Cortisol levels during the OGTT correlated negatively with WHR. The ratio of these Cortisol determinations correlated positively with the body-mass index (BMI) (r = 0.554; P < 0.001), WHR (r = 0.536; P < 0.001), TG (r = 0.397; P = 0.001), fasting insulin (r = 0.534; P < 0.001) and C-peptide (r = 0.458; P < 0.001), and negatively with HDLC (r = 0.353; P = 0.004). In multiple regression analyses, BMI and the 2-h ACTH response to glucose were significant predictors of WHR and, in addition, the Cortisol ratio, WHR, and BMI of insulin. Conclusions. Abdominal obesity may be associated with subtle central adrenal insufficiency, which might also affect insulin and lipoprotein metabolism.     

Assessment of preferred methods to measure insulin resistance in Asian patients with hypertension

Insulin resistance (IR), a metabolic risk factor, is linked to the pathogenetic mechanism of primary hypertension. Detecting IR in the patients with hypertension will help to predict and stratify the added cardiovascular risk, institute appropriate IR management, and manage hypertension optimally. There are many methods for assessing IR, each with distinct advantages and disadvantages. The euglycemic insulin clamp and intravenous glucose tolerance test, gold standards for measuring IR, are used in research but not in clinical practice. Homeostatic model assessment (HOMA‐IR), a method for assessing β‐cell function and IR, is frequently applied presently, particularly in Asia. Besides, the triglyceride–glucose index (TyG) first published by South American authors showed a good correlation with the insulin clamp technique and HOMA‐IR index. This simple, convenient, and low‐cost TyG index is of research interest in many countries in Asia and can be used to screen for IR in the Asian hypertensive community.     

胰岛素、血脂与高血压及动脉粥样硬化关系的实验研究

选用40只雄性高血压大鼠（SHR）为实验模型。探讨了胰岛素、血脂与高血压及动脉粥样硬化的关系。结果显示：高脂组SHR的收缩压、空腹血清胰岛素、血清甘油三脂、总胆固醇及丙二醛水平，肝脏和主动脉胆固醇含量显著高于对照组SHR.叠加组显著高于高脂组。血清高密度脂蛋白胆固醇与总胆固醇比值、卵磷脂胆固醇酞基转移酶、胰岛素敏感性指数及超氧化物歧化酶活力低于对照组。叠加组显著高于高脂组。除对照组外，各组主动脉标本光镜及电镜下可见典型动脉粥样硬化病变。提示，SHR存在明显胰岛素抵抗、高胰岛素血症及脂质代谢紊乱；长期皮下注射胰岛素则加重其紊乱；高血压及高脂膳食有协同作用。     

The role of C-reactive protein,adiponectin and leptin in the association between abdominal adiposity and insulin resistance in middle-aged individuals

Background and aimsIn the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance.Methods and resultsIn this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm² and aSAT of 300 (111) cm². Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59–70), 33% (95%CI: 28–42) and 20% (95%CI: 14–26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women.ConclusionWhere leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.     

Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin

Aging is an independent risk factor for hypertension, and hypertension and insulin resistance commonly coexist in the elderly. This study was designed to examine the effects of aging-related insulin resistance on blood pressure (BP) and its underlying mechanisms, with specific focus on the role of exercise in reversing hypertensive response. Adult (6-month-old) and aging (24-month-old) male Sprague-Dawley rats were subjected to a 10 weeks free-of-loading swim training (60 min/day, 5 days/week). Arterial vasorelaxation, cardiac contraction, eNOS activation, and iNOS and gp91^phox expression were determined. Under aging-related insulin resistance conditions, insulin infusion significantly elevated BP (P < 0.05). Aging caused significant endothelial dysfunction (P < 0.05 − 0.01), which was responsible for decreased arterial vasorelaxation to insulin. Aging attenuated myocardial contractile response to insulin, decreased eNOS expression and its phosphorylation by insulin, and increased iNOS and gp91^phox expression in aging arteries (P < 0.01). Exercise improved insulin sensitivity, potentiated insulin’s positive inotropic effects, facilitated arterial vasorelaxation to insulin, increased arterial eNOS activation in adult and aging rats, and thus attenuated insulin resistance-related hypertensive response to insulin. Moreover, exercise markedly reversed increased iNOS and gp91^phox expression in aging arteries. Inhibition of eNOS with Cavtratin or L-NAME significantly blocked exercise-facilitated arterial vasorelaxation to insulin and exercise-lowered BP response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin, but not insulin’s positive inotropic effects, plays an important role in the development of aging-related hypertension. The reversal of hypertensive response to insulin by exercise is most likely associated with improved insulin sensitivity in an eNOS-dependent manner and reduced oxidative and nitrative stresses. Electronic supplementary material:  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Returned for 1. Revision: 18 February 2008 1. Revision received: 11 August 2008 Returned for 2. Revision: 10 September 2008 2. Revision received: 15 September 2008