Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance

OBJECTIVE: We investigated subcutaneous adipose tissue expression of FOXC2 and selected genes involved in brown adipogenesis in adult human subjects in whom we have previously identified a reduced potential of precursor cell commitment to adipose-lineage differentiation in relation to insulin resistance. Research Methods and Procedure: Gene expression was studied using quantitative real time polymerase chain reaction. The relation between the expression of brown adipogenic genes and the genes involved in progenitor cell commitment, adipose cell size, and insulin sensitivity in vivo was analyzed. RESULTS: The expression of FOXC2, MASK, MAP3K5, retinoblastoma protein (pRb), peroxisome proliferator-activated protein gamma (PPARgamma), and retinoid X receptor gamma (RXRgamma) was decreased in the insulin-resistant compared with insulin-sensitive subjects, whereas PPARgamma-2 and CCAAT/enhancer binding protein alpha (C/EBPalpha) showed no differential expression. The FOXC2 expression correlated with that of Notch and Wnt signaling genes, as well as of the genes studied participating in brown adipogenesis, including MASK, MAP3K5, PPARgamma, pRb, RXRgamma, and PGC-1. A second-level correlation between PPARgamma and UCP-1 was also significant. In addition, the expression of MASK, MAP3K5, pRb, RXRgamma, and PGC-1 inversely correlated with adipose cell mass and also correlated with the glucose disposal rate in vivo. DISCUSSION: Our results suggest that a reduced brown adipose phenotype is associated with insulin resistance and that a basal brown adipose phenotype may be important for maintaining normal insulin sensitivity.     

Glucose metabolism and insulin sensitivity in patients with Turner syndrome treated with growth hormone

The authors investigated the effect of growth hormone treatment on 20 Turner syndrome patients. The aim was to assess glucose and insulin responses to oral glucose loading in 9 prepubertal and 11 pubertal patients with Turner syndrome. Thirty eight healthy subjects matched for chronological age and BMI were selected as controls. Similar glucose responses were observed in the prepubertal and postpubertal patients groups and no difference was found between patients and controls. No correlation was observed between glycaemic control of insulin sensitivity and growth hormone treatment. Although the supraphysiological doses of growth hormone did not result in substantial impairement in glucose tolerance, it is concluded that hyperinsulinaemia could be a consequence of the treatment and regular check up for glycaemic control is needed in these patients.     

Flow-type pulsatile cytofluorometer with increased sensitivity

A new cytofluorometer is described, with sensitivity twice as high as that of the existing units.     

老年高血压合并腔隙性脑梗塞患者胰岛素敏感性的临床研究

目的 研究胰岛素敏感指数(ISI)改变与高血压合并腔隙性脑梗塞之间的关系.方法 选取33例高血压合并腔隙性脑梗塞患者作为研究对象,测定空腹血糖(FPG)、胰岛素(Ins)、C-肽、总胆固醇(TC)、甘油三酯(TG).另33例老年高血压病患者作为对照组,同时采用李光伟等提出的ISI方法进行胰岛素抵抗(IR)计算.结果 高血压合并腔隙性脑梗塞患者Ins、C-肽水平显著高于对照组(P＜0.01),其ISI较对照组显著降低(P＜0.01).结论 老年高血压合并腔隙性脑梗塞ISI明显降低,存在IR,IR作为腔隙性脑梗塞独立危险因素应引起高度重视.     

老年高血压合并腔隙性脑梗塞患者胰岛素敏感性的临床研究

目的研究胰岛素敏感指数（ISI）改变与高血压合并腔隙性脑梗塞之间的关系。方法选取33例高血压合并腔隙性脑梗塞患者作为研究对象,测定空腹血糖（FPG）、胰岛素（Ins）、C-肽、总胆固醇（TC）、甘油三酯（TG）.另33例老年高血压病患者作为对照组,同时采用李光伟等提出的ISI方法进行胰岛素抵抗（IR）计算。结果高血压合并腔隙性脑梗塞患者Ins、C-肽水平显著高于对照组（P〈0.01）,其ISI较对照组显著降低（P〈0.01）。结论老年高血压合并腔隙性脑梗塞ISI明显降低,存在IR,IR作为腔隙性脑梗塞独立危险因素应引起高度重视。     

酒精对大鼠胰岛素敏感性和骨骼肌胰岛素受体底物mRNA表达的影响

目的　从基因表达水平探讨摄入不同剂量酒精影响胰岛素敏感性的分子机制。方法清洁级Wistar大鼠 80只 ,雌雄各半 ,随机分为对照组和低、中、高剂量组 ,摄入酒精剂量分别为每日 0、0 6、1 8和 3 0ml/kg。给予酒精 13周后 ,测定空腹血糖和血胰岛素 ,计算HOMA胰岛素抵抗指数(HOMA IR)。提取骨骼肌组织总RNA ,通过逆转录 聚合酶链反应测定胰岛素受体底物 1(IRS 1)mRNA表达水平。结果　雌性大鼠 3 0ml/kg组空腹血糖为 (8 36± 0 5 7)mmol/L ,空腹血胰岛素为(15 2 5±3 32 )mIU/L ,0 6ml/kg组HOMA IR为 1 775 3± 0 1381,IRS 1mRNA表达水平为 0 76 6 1± 0 0 76 9;0 8ml/kgHOMA IR为 2 2 0 2 2± 0 2 710 ,IRS 1mRNA表达水平为 0 5 0 18± 0 0 4 92 ;3 0ml/kg组HOMA IR(1 85 0 1± 0 16 2 8)与对照组 (1 982 6± 0 12 4 6 )相比 ,差异无统计学意义 ,IRS 1mRNA表达水平为0 4 181± 0 0 4 91。雄性大鼠 3 0ml/kg组空腹血糖为 (8 12± 0 72 )mmol/L ,空腹血胰岛素为 (18 6 5±4 2 4 )mIU/L ,仅 0 8ml/kg组HOMA I为 (1 8785± 0 2 5 0 2 ) ,IRS 1mRNA表达水平为 0 82 4 9± 0 0 6 4 7。结论　适量酒精摄入可以增强胰岛素敏感性 ,从而降低 2型糖尿病的发病危险。而长期过量酒精摄入可以降低     

Discipline-specific insulin sensitivity in athletes

ObjectiveWeight status and abnormal liver function are the two factors that influence whole-body insulin sensitivity. The main goal of the study was to compare insulin sensitivity in athletes (n = 757) and physically active controls (n = 670) in relation to the two factors.MethodsHomeostatic metabolic assessment for insulin resistance (HOMA-IR), weight status, and abnormal liver function (alanine aminotransferase and aspartate aminotransferase) were determined from 33 sports disciplines under morning fasted condition. This study was initiated in autumn 2006 and repeated in autumn 2007 (n = 1508) to ensure consistency of all observations.ResultsIn general, HOMA-IR and blood pressure levels in athletes were significantly greater than those in physically active controls but varied widely with sport disciplines. Rowing and short-distance track athletes had significantly lower HOMA-IR values and archery and field-throwing athletes had significantly higher values than the control group. Intriguingly, athletes from 22 sports disciplines displayed significantly greater body mass index values above control values. Multiple regression analysis showed that, for non-athlete controls, body mass index was the only factor that contributed to the variations in HOMA-IR. For athletes, body mass index and alanine aminotransferase independently contributed to the variation of HOMA-IR.ConclusionThis is the first report documenting HOMA-IR values in athletes from a broad range of sport disciplines. Weight status and abnormal liver function levels appear to be the major contributors predicting insulin sensitivity for the physically active population.     

Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following l-arginine supplementation

Purpose

The aim of this study is to evaluate the long-term influence of l-arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result.

Methods

A randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of l-arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used.

Results

We found that 6 months of l-arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P < 0.01) and zinc levels (Δ1.5 μmol/L, P < 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed (R = 0.80, P < 0.01). In the group of patients treated with l-arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted (R = ?0.38, P < 0.05).

Conclusions

l-Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.     

Increased insulin sensitivity in iron-deficient rats

Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.