Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure

Aims/hypothesis Hypertrophic and failing hearts have increased utilisation of glucose, but also develop insulin resistance and reduced ability to produce ATP. Increased levels of the IL-6-related cytokine leukaemia inhibitory factor (LIF) are found in failing hearts, and we have recently shown that LIF reduces ATP production in isolated cardiomyocytes. In the present study we investigated effects of LIF on glucose metabolism, and how LIF-treated cells respond to insulin stimulation. Methods Cardiomyocytes were isolated from adult Wistar rats by collagen digestion, maintained in culture for 48 h, and then treated with 1 nmol/l LIF. Results Acute LIF treatment increased deoxyglucose uptake compared with controls, but no additive effect was observed in cardiomyocytes treated with LIF and insulin. The phosphatidylinositol 3-kinase inhibitor wortmannin did not affect LIF-induced glucose uptake. LIF had no effect on AMP-activated protein kinase phosphorylation. Cardiomyocytes treated with LIF for 48 h did not respond to insulin by increasing deoxyglucose uptake and showed a reduced insulin-mediated uptake of oleic acid and formation of complex lipids compared with control cells. Chronic LIF treatment increased gene expression of the suppressor of cytokine signalling (Socs) 3 and reduced expression of solute carrier family 2, member 4 (Slc2a4, previously known as glucose transporter 4 [Glut4]). In line with these observations, chronic LIF treatment reduced insulin-mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase (GSK)-3. Conclusions/interpretation Acute LIF treatment increased glucose uptake in isolated cardiomyocytes by a pathway different from that of insulin. Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin-mediated phosphorylation of GSK-3 and Akt/PKB.     

Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study

Aims/hypothesis In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA_1c; secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia. Methods In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA_1c ≥8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. Results During the last 12 weeks, FPGs averaged 5.75±0.02 and 5.96±0.03 mmol/l (p<0.001) and insulin doses were 68±5 and 70±6 IU/day (0.69±0.05 and 0.66±0.04 IU kg^–1 day^–1, NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA_1c was 7.14±0.12 and 7.16±0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1±0.8 episodes/patient-year) than in the NPH+MET group (9.0±2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1±0.3 mmol/l) than in the G+MET group (8.6±0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA_1c <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7±0.2 vs 6.7±0.3 mmol/l for patients reaching vs those not reaching target, p<0.01). Conclusions/interpretation Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinnertime hyperglycaemia compared with NPH+MET.     

紫外线照射充氧液体疗法对肺心病患者血流动力学的影响

目的　观察紫外线照射充氧液体疗法（ＵＤＩＯ） 治疗肺心病对患者肺血流动力学的影响。方法　对经ＵＤＩＯ 疗法治疗的患者３７ 例及对照组３２ 例,检测治疗前后肺阻抗、心阻抗及二者的微分图,并进行比较分析。结果　ＵＤＩＯ 组治疗后平均肺动脉压明显下降由（３ ．５２ ±０．４８） ｋＰａ 降至（２ ．４３ ±０ ．７２） ｋＰａ（ Ｐ＜０ ．０５） ,对照组也呈下降趋势,由（３．３９±０ ．５５） ｋＰａ 降至（２ ．９１ ±０ ．４５） ｋＰａ,但差异无显著性。治疗前后平均肺动脉压差值,两组比较差异有显著性（ Ｐ＜ ０ ．０５） ;心功能两组治疗前后的组内比较差异均有显著性（ Ｐ＜ ０．０５） ,但治疗前后差值组间差异无显著性。结论　ＵＤＩＯ 疗法对降低肺心病患者动脉压有显著疗效,值得临床推广应用。     

云南省彝族三种常见葡萄糖-6-磷酸脱氢酶基因突变型分析

目的分析云南籍彝族葡萄糖６磷酸脱氢酶（Ｇ６ＰＤ）缺乏症患者三种常见基因突变型。方法应用突变特异性扩增系统（ＡＲＭＳ）分析２８例云南籍彝族Ｇ６ＰＤ缺乏症患者Ｇ６ＰＤ基因突变类型。结果发现１３８８（Ｇ→Ａ）突变１２例,１３７６（Ｇ→Ｔ）突变９例,９５（Ａ→Ｇ）突变１例,未定型６例。结论在彝族人群中检出１３７６和９５突变在国内尚属首次。上述三种突变在２８例彝族Ｇ６ＰＤ缺乏症患者中占７８６％,且也为汉族中的常见突变,结果提示汉族和彝族可能源于同一祖先,云南省彝族的形成可能是在Ｇ６ＰＤ基因常见突变产生之后,为研究彝族的起源提供了分子遗传学资料。     

葡萄糖-6-磷酸脱氢酶基因G487A突变型研究

目的　鉴定中国白族和傣族人群中的葡萄糖６磷酸脱氢酶（Ｇ６ＰＤ）Ｇ４８７Ａ 基因突变型,为少数民族Ｇ６ＰＤ缺乏症的防治提供理论指导;为研究分子进化、民族起源及迁移提供遗传学资料。方法　对云南白族、傣族、汉族及广西汉族的Ｇ６ＰＤ缺乏症患者进行聚合酶链反应限制性内切酶分析（ＰＣＲＲＥ） ,聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ） 及ＤＮＡ序列分析。结果　首次在白族及傣族人群中发现Ｇ６ＰＤＧ４８７Ａ基因突变型。６６ 例白族患者中发现６ 例,５２ 例傣族患者中发现１ 例Ｇ４８７Ａ 突变;检查４６ 例广西汉族患者未发现该突变。Ｇ６ＰＤＧ４８７Ａ基因突变型的个体在无诱因作用时,其血红蛋白含量、红细胞计数及网织红细胞计数基本正常。结论　Ｇ６ＰＤＧ４８７Ａ 基因突变型多属Ｇ６ＰＤ 缺乏症临床Ⅲ型;该突变型是汉族、白族和傣族共同具有的基因突变型。提示：中华民族可能同源     

糖尿病患者血清低密度脂蛋白亚组分的分布及氧化易感性

为探讨糖尿病（ＤＭ）患者血浆低密度脂蛋白（ＬＤＬ）亚组分的异常特性。本文采用密度工超速离心直接分离ＬＤＬ亚组分,并对其分布及体外铜离子介导的氧化易感性进行分析。结果表示单纯ＤＭ患者、ＤＭ合并症患者及对照组间ＬＤＬ亚组分分布无差别;ＤＭ患者ＬＤＬ各组分氧化延滞时间显著缩短,尤以ＤＭ合并症患者明显,示其易于氧化,血浆脂质巡氧化程度亦增高。认为ＤＭ患者动脉粥样硬化的高发生率同其ＬＤＬ易于氧化的我相关联。     

雾化吸入布地奈德治疗AECOP D合并2型糖尿病患者疗效及对肺通气功能和糖代谢的影响

目的 分析雾化吸入布地奈德治疗慢性阻塞性肺疾病急性加重(AECOPD)合并2型糖尿病(T2DM)患者疗效及对肺通气功能和糖代谢指标的影响.方法 选择四川大学华西医院2019年1月至2020年5月诊治的120例AECOPD合并T2DM患者作为对象,根据非随机临床同期对照研究及患者自愿原则分为对照组58例和观察组62例,其...     

The role of hyperglycaemia in the development of diabetic cardiomyopathy

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腹部推拿对高脂饮食诱发肥胖大鼠胰岛素抵抗的改善作用机制

目的:观察腹部推拿对肥胖大鼠胰岛素抵抗的改善作用与机制.方法:将60只大鼠随机分为空白对照组和模型组,空白对照组喂养普通饲料;模型组喂养高脂饲料造模,造模成功大鼠随机分为模型对照组和推拿干预组.两组均继续采用高脂饲料喂养,推拿干预组采用腹部推拿疗法进行干预.4周后观察各组动物空腹血糖(FPG)、总胆固醇(TC)、甘油三...