The insulin receptor family in the heart: new light on old insights

Insulin was discovered over 100 years ago. Whilst the first half century defined many of the physiological effects of insulin, the second emphasised the mechanisms by which it elicits these effects, implicating a vast array of G proteins and their regulators, lipid and protein kinases and counteracting phosphatases, and more. Potential growth-promoting and protective effects of insulin on the heart emerged from studies of carbohydrate metabolism in the 1960s, but the insulin receptors (and the related receptor for insulin-like growth factors 1 and 2) were not defined until the 1980s. A related third receptor, the insulin receptor-related receptor remained an orphan receptor for many years until it was identified as an alkali-sensor. The mechanisms by which these receptors and the plethora of downstream signalling molecules confer cardioprotection remain elusive. Here, we review important aspects of the effects of the three insulin receptor family members in the heart. Metabolic studies are set in the context of what is now known of insulin receptor family signalling and the role of protein kinase B (PKB or Akt), and the relationship between this and cardiomyocyte survival versus death is discussed. PKB/Akt phosphorylates numerous substrates with potential for cardioprotection in the contractile cardiomyocytes and cardiac non-myocytes. Our overall conclusion is that the effects of insulin on glucose metabolism that were initially identified remain highly pertinent in managing cardiomyocyte energetics and preservation of function. This alone provides a high level of cardioprotection in the face of pathophysiological stressors such as ischaemia and myocardial infarction.     

依托咪酯联合右美托咪定对高血压基底节区脑出血患者脑糖氧代谢和氧化应激的影响

摘要 目的：观察依托咪酯联合右美托咪定对高血压基底节区脑出血患者脑糖氧代谢和氧化应激的影响。方法：纳入2020年1月-2022年12月期间我院收治的90例高血压基底节区脑出血患者,采用随机数字表法将患者分为对照组和研究组,各为45例。对照组患者接受依托咪酯乳状注射液麻醉,研究组患者接受依托咪酯乳状注射液联合右美托咪定注射液麻醉。对比两组血流动力学[心率（HR）、平均动脉压（MAP）]、糖氧代谢指标[氧饱和度（SjvO₂）、脑氧摄取率（CEO₂）、脑动静脉氧差（AVDO₂）]、氧化应激指标[丙二醛（MDA）和超氧化物歧化酶（SOD）]和不良反应。结果：麻醉诱导后5 min（T1）~手术完毕时（T4）时间点,研究组心率（HR）、平均动脉压（MAP）低于对照组（P<0.05）。T4时间点,研究组SjvO₂高于对照组,CEO₂、AVDO₂低于对照组（P<0.05）。T4时间点,研究组SOD高于对照组,MDA低于对照组（P<0.05）。两组不良反应总发生率对比未见差异（P>0.05）。结论：依托咪酯联合右美托咪定可更好维持机体血流动力学,改善脑糖氧代谢,减轻氧化应激,对高血压基底节区脑出血患者发挥出良好的麻醉效果。     

Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease

Dyslipidemia is an important risk factor for cardiovascular disease (CVD) and atherosclerosis. When dyslipidemia coincides with other metabolic disorders such as obesity, hypertension, and glucose intolerance, defined as the metabolic syndrome (MS), individuals present an elevated risk to develop type 2 diabetes (T2D) as well as CVD. Because the MS epidemic represents a growing public health problem worldwide, the development of therapies remains a major challenge. Alterations of bile acid pool regulation in T2D have revealed a link between bile acid and metabolic homeostasis. The bile acid receptors farnesoid X receptor (FXR) and TGR5 both regulate lipid, glucose, and energy metabolism, rendering them potential pharmacological targets for MS therapy. This review discusses the mechanisms of metabolic regulation by FXR and TGR5 and the utility relevance of natural and synthetic modulators of FXR and TGR5 activity, including bile acid sequestrants, in the treatment of the MS.     

A bioelectrochemical study of a suspension of Escherichia coli cells metabolizing glucose and lactose

The metabolism of glucose and lactose in Escherichia coli K-12 cells has been studied using a bioelectrochemical (BEC) approach. The magnitude and the duration of the response of a BEC anode were found to be functions of the composition of nutrient media and the concentration of bacterial cells. The amount of electricity that is generated enzymatically during the metabolism of a particular substrate depends on the activity of the relevant enzymes. This suggests that the BEC approach can be used for evaluating the activity of particular enzyme systems.     

Variability in factors causing light attenuation in Lake Victoria

1. The major optical components controlling the attenuation of photosynthetic available radiation in nearshore areas of Lake Victoria (Uganda and Kenya) were examined and their impact compared. It was found that chromophoric dissolved organic matter and tripton play a dominating role in many nearshore areas, indicating that the coastal areas of Lake Victoria cannot be considered as Case I waters.
2. Concentrations of chromophoric dissolved organic matter declined with distance from the coast in an exponential manner indicating dilution and degradation of terrestrial sources of organic matter rather than in situ production. The importance of tripton was found to follow a similar pattern, while the relative importance of phytoplankton biomass in overall attenuation of photosynthetic available radiation was found to increase with distance from the coast. A specific attenuation coefficient for phytoplankton biomass was determined (0.019 m² mg Chl a ⁻¹).
3. Using a light limitation approach based on carrying capacity, it was possible to map areas that are closer to being light limited. Light limitation appears to occur throughout most bays and some coastal areas receiving catchment waters. This spatial information, geographically referenced to bathymetric and catchment conditions, was utilized to understand the importance of environmental conditions in limiting phytoplankton biomass.     

Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach

The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT₇ receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions.     

人血管内皮细胞中腺苷代谢的定量研究

目的:通过对人脐静脉内皮细胞腺苷分泌进行定性及定量研究,了解人类血管内皮细胞的腺苷代谢及机制.方法:收集并测定不同干预下细胞柱流出液中分离的人脐静脉内皮细胞分泌的腺苷量.结果:在无干预、抑制腺苷激酶及去氨酶、抑制细胞膜腺苷转运情况下,人脐静脉内皮细胞腺苷分泌率分别为13.5±7.1 pmol·min-1·mg-1、32.5±14.2 pmol·min-1·mg-1和20.8±15.7 pmol·min-1·mg-1.结论:人类血管内皮细胞内腺苷合成高于胞外,而细胞膜腺苷转运被抑制后的腺苷分泌率反而高于生理状态下分泌率,则表明腺苷在胞内分解代谢非常迅速,使部分腺苷反由胞外扩散入胞内.     

基于MuSIASEM理论的大连经济技术开发区可持续发展评价

基于社会生态系统代谢多尺度综合评估（MuSIASEM）理论,对2000-2007年大连经济技术开发区人类活动时间、体外能投入量和增加值进行综合评价.结果表明：2000-2007年,大连开发区居民生活水平逐年提高;农业逐渐萎缩;第二产业仍为区域支柱产业,能耗较大;第三产业发展落后于第二产业;区域整体和各个产业的体外能代谢率明显提高,能源密度不断下降;人类活动时间与体外能投入量不断减少的情况下,经济增加值稳步增长,区域整体发展呈可持续态势.     

基于"经筋理论"针刀治疗对早中期膝骨关节炎患者骨代谢指标和血清TIMP-1、MMP-3、MMP-13的影响

摘要 目的：探讨基于"经筋理论"针刀治疗对早中期膝骨关节炎（KOA）患者骨代谢指标和血清金属蛋白酶抑制物-1（TIMP-1）、基质金属蛋白酶（MMP）-3、MMP-13的影响。方法：根据随机数字表法,将2021年1月至2023年1月期间就诊于新疆医科大学附属第一医院的120例早中期KOA患者分为对照组（n=60,常规治疗）和研究组（n=60,对照组的基础上接受"经筋理论"针刀治疗）。对比两组疗效、量表评分[疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎调查表（WOMAC）]、骨代谢指标[抗酒石酸盐酸性磷酸酶异构体（TRACP-5b）、骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）]和血清TIMP-1、MMP-3、MMP-13。结果：与对照组相比,研究组的临床总有效率更高（P<0.05）。与对照组相比,研究组治疗后WOMAC、VAS评分和血清MMP-3、MMP-13、TRACP-5b水平更低,TIMP-1、BALP、BGP水平更高（P<0.05）。结论：基于"经筋理论"针刀治疗早中期KOA患者,可有效减轻疼痛症状,提高临床治疗效果,可能与改善骨代谢指标和血清TIMP-1、MMP-3、MMP-13水平有关。