Effects of over-expressing resistin on glucose and lipid metabolism in mice

Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role ofresistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose （GLU） levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol （TC） level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid （FFA） and high density lipoprotein （HDL） cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride （TG） levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.     

葛根素对脂肪细胞糖脂代谢作用研究

探讨葛根素对脂肪细胞糖、脂代谢的影响.建立3T3-L1脂肪细胞IR模型,葡萄糖氧化酶法测定葛根素处理48 h后培养液中葡萄糖残存量、铜试剂显色法测定游离脂肪酸浓度.与模型组比较,葛根素高、低剂量组葡萄糖消耗量显著增加(P<0.05),游离脂肪酸水平呈现降低趋势.葛根素明显增加脂肪细胞的葡萄糖消耗,对TNF-α诱导的脂肪分解无明显作用.     

人参水提物对小鼠血糖及血脂代谢的影响

研究了人参水提物对正常小鼠血糖和血脂代谢的影响及其对四氧嘧啶(ALX)致糖尿病小鼠降血糖的作用.实验证实,200和400 mg/kg人参水提物极显著地降低了血糖;100 mg/kg水提物能够显著降低血清甘油三酯(P＜0.05),且随着剂量的增加,呈现上升的趋势.200 与400 mg/kg人参水提物均能显著降低正常小鼠餐后30 min的血糖值(P＜0.05).另外,人参水提物灌胃给糖尿病小鼠,均能降低血糖,其中300 mg/kg效果最显著(P＜0.01).研究结果表明:人参水提物可能是通过促进小鼠体内的葡萄糖转化成甘油三脂,调节了物质代谢中血糖与血清甘油三酯的相互转化.同时,人参水提物还具有改善正常小鼠的葡萄糖耐量,降低糖尿病小鼠血糖值的作用.     

白藜芦醇对胰岛素抵抗小鼠糖脂代谢的影响及心肌的保护作用

为研究白藜芦醇(RES)对胰岛素抵抗小鼠的糖脂代谢影响及心肌的保护作用。将雄性c57bl/6小鼠随机分对照组(NC)、高脂组(H)、高脂+溶媒(C)、高脂+溶媒+RES干预组(R),分别给予相应饲料喂养14周后给予相应灌胃干预处理。8周后检测小鼠血脂、血糖、血清脂肪因子;检测心肌羟脯氨酸;采用蛋白质印迹法(western blotting,WB)检测心肌Ⅰ、Ⅲ型胶原的蛋白表达;实时荧光定量PCR、WB检测小鼠的心肌PPARγ(过氧化物酶增殖物激活受体γ)、ADPN(脂联素)、TNF-α(肿瘤坏死因子α)的mRNA及蛋白表达情况。结果表明:与NC组相比,H组与C组总胆固醇(total cholesteral,TC)、低密度脂蛋白(low density lipoprotein,LDL)升高(P0.01);血清瘦素、抵抗素水平升高;心肌中羟脯氨酸、胶原、TNF-α升高(P0.01或P0.05);PPARγ、ADPN表达下降(P0.01);而R组较H组TC、LDL降低(P0.05);血清瘦素、抵抗素水平下降;心肌中胶原、TNF-α降低(P0.01或P0.05);PPARγ、ADPN的表达升高(P0.01)。RES可能是通过激动PPARγ调节ADPN、TNF-α改善胰岛素抵抗小鼠糖脂代谢紊乱、心肌肥厚、纤维化。     

大豆异黄酮对卵巢切除大鼠糖脂代谢和血清瘦素、抵抗素表达的影响

为探讨大豆异黄酮对卵巢切除大鼠糖脂代谢和血清瘦素、抵抗素表达的影响,将12周SD大鼠分成3组,假手术(Sham)组、卵巢切除(OVX)组和大豆异黄酮(OVX+Gen)组,每组7只,卵巢切除术后10 d,OVX组和Sham组大鼠每天腹腔注射生理盐水0.1 ml/只,OVX+Gen组每天注射大豆异黄酮0.2 mg/只,连续注射30 d后处死取血,检测子宫病理改变、血糖血脂和胰岛素水平、血清瘦素和抵抗素含量.结果发现卵巢切除后大鼠总胆固醇、HDL和LDL均增加(P<0.05),但胰岛素、血糖、甘油三酯、血清瘦素和抵抗素水平变化不明显(P>0.05);卵巢切除后补充大豆异黄酮,可促进子宫内膜上皮部分增生,但胰岛素、血糖、总胆固醇、甘油三酯、LDL和HDL、血清瘦素和抵抗素水平均无明显变化(与OVX组相比,P>0.05),结果提示大豆异黄酮对卵巢切除大鼠糖脂代谢参数和血清瘦素、抵抗素水平影响不大.     

Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase

Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth. Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation, little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD(+)-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.     

Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye

The Drosophila eye, a paradigm for epithelial organization, is highly polarized with mirror-image symmetry about the equator. The R3 and R4 photoreceptors in each ommatidium are vital in this polarity; they adopt asymmetrical positions in adult ommatidia and are the site of action for several essential genes. Two such genes are frizzled (fz) and dishevelled (dsh), the products of which are components of a signalling pathway required in R3, and which are thought to be activated by a diffusible signal. Here we show that the transmembrane receptor Notch is required downstream of dsh in R3/R4 for them to adopt distinct fates. By using an enhancer for the Notch target gene Enhancer of split mdelta, we show that Notch becomes activated specifically in R4. We propose that Fz/Dsh promotes activity of the Notch ligand Delta and inhibits Notch receptor activity in R3, creating a difference in Notch signalling capacity between R3 and R4. Subsequent feedback in the Notch pathway ensures that this difference becomes amplified. This interplay between Fz/Dsh and Notch indicates that polarity is established through local comparisons between two cells and explains how a signal from one position (for example, the equator in the eye) could be interpreted by all ommatidia in the field.     

Insulin stimulation of glucose uptake can be mediated by diacylglycerol in adipocytes

An early effect of insulin in adipocytes is to stimulate glucose uptake. The increased uptake appears to be due to mobilization of glucose transporters from an intracellular location to the plasma membrane and to enhanced intrinsic activity of the transporters. Little is known about the insulin-generated signals causing these changes. Phorbol esters have been shown to mimic the insulin effect, but phosphorylation of the transporter does not seem to be involved. A phospho-oligosaccharide was recently shown to mimic the effects of insulin on protein phosphorylation, suggesting that it could be a mediator for some intracellular metabolic effects of the hormone, but it did not affect glucose uptake. A diacyglycerol is produced in the plasma membrane in conjunction with the generation of the phospho-oligosaccharide. Here I show that added 1,2-diacylglycerols potently increase glucose transporter-mediated uptake of glucose in rat adipocytes, but without activation of protein kinase C.