Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Diagnostic sensitivity of electrophysiology and ultrasonography in ulnar neuropathies of different severity

ObjectiveTo assess the diagnostic performance of electrophysiology and nerve ultrasound in ulnar neuropathies of varying clinical severity in 135 consecutive patients.MethodsClinical severity of ulnar neuropathy was graded on a 4 point scale from very mild (symptoms only) to severe (marked atrophy of intrinsic hand muscles). Sensitivity and localization ability of electrophysiology and nerve ultrasound were assessed for each point of the scale.ResultsUltrasound had higher sensitivity than electrophysiology in clinically very mild (20% and 3% for ultrasound and electrophysiology, respectively) and mild (62% and 47% for ultrasound and electrophysiology, respectively) neuropathies, had greater localizing ability in axonal ulnar neuropathies, and identified nerve hypermobility.Ultrasound nerve cross-sectional area had strong positive correlation with both clinical and electrophysiological severity scores, but with significant overlap across the severity groups.ConclusionThe diagnostic work-up of ulnar neuropathies was improved by using both electrophysiology and ultrasound at all levels of clinical severity. Ultrasound increased the diagnostic yield in very mild and mild neuropathies, localized all the ulnar neuropathies with abnormal non-localizing electrophysiology and identified nerve hypermobility.SignificanceThis is the first detailed analysis of the diagnostic performance of electrophysiology and ultrasound in ulnar neuropathies of varying severity.     

食蟹猴年龄相关的运动功能减退及其与纹状体多巴胺转运体的关系

目的研究食蟹猴老化过程中运动行为和脑内纹状体多巴胺系统功能变化及两者之间的相关关系。方法选取4岁、10岁和15岁3个年龄组的健康食蟹猴共29只,利用计算机化的网络摄像头视频检测系统和行为分析软件连续采集和分析每个动物8h随意运动活动总量,各年龄组分别选取4只动物用多巴胺转运体(DAT)配体99mTc-TRODAT-1结合单光子发射体层摄影术(SPECT)显像观察脑内纹状体多巴胺转运体放射性摄取率的变化。结果在4岁、10岁和15岁年龄组,8h随意运动活动总量(×106)分别为5·00±1·93,3·28±1·02,2·79±0·67,在10岁和15岁较之4随年龄组分别降低了34·50%和55·71%(P<0·05,P<0·01),但此两个年龄组运动活动总量无显著差异(P>0·05);纹状体99mTc-TRODAT-1放射性摄取率分别为2·98±0·08,2·56±0·12和2·27±0·35,10岁和15岁较之4随年龄组分别降低了14·00%和25·60%,但仅4岁与15岁年龄组存在显著相关关系(P<0·01)。二者均随着年龄的增长呈逐渐减低的趋势,直线回归分析显示两者分别与年龄呈负相关关系(r=-0·57,P=0·001;r=-0·86,P<0·01)。8h随意运动活动总量与纹状体99mTc-TRODAT-1放射性摄取率呈显著的正相关关系(r=0·70,P<0·05)。结论正常食蟹猴老化过程中,脑内多巴胺神经系统功能的减退伴随着运动行为的减少,两者之间的相关关系进一步佐证了运动功能的减退可能是由于纹状体内多巴胺神经元功能减退所致。     

Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

Summary The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10^–9–10^–6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect. Send offprint requests to O. Binah at the above address     

On the physical properties of red cell ghost membranes in the affective disorders and psychoses A fluorescence polarization study

Membrane order was measured in the erythrocyte ghost membranes of DSM-III schizophreniform disorder (SF), DSM-III schizophrenic (SCZ) and DSM-III manic (bipolar) (M) patients and a group of age- and sex-matched controls. Fluorescence polarization with the probe 1,6-diphenyl1-1,3,5-hexatriene was used to determine the steady-state fluorescence anisotropy (r_s). The SF group showed a significant increase in r_s (Δr_s = 0.037) from the control group. Although the means were not significantly different, 3 of 8 Ms and 5 of 8 SCZs also had r_s values > the highest control value. Thermotropic behavior of the membranes was evaluated over the range of 40 to 20°C. No difference among groups in membrane enthalpy was detected. Thus, the differences in r_s appear to be associated with differences in entropy. Phosphatidylcholine (PC) levels, which were known to be abnormal in these patients, were compared with the r_s values. A significant (P < 0.001, R= -0.63) linear correlation between r_s and membrane PC levels was observed. Overall these data further support the view that unusual membrane biophysical factors may occur with high frequency in the psychoses and affective disorders.     

腺嘌呤核苷酸载体的功能和表达与心力衰竭

腺嘌呤核苷酸载体（ANT）是一种位于线粒体内膜上的转运蛋白，它在组织细胞能量产生和消耗的耦联中起关键性作用。作者就ANT的功能和表达情况及其与心力衰竭之间的关系作一综述。     

An alternative mechanism of actions for neuroleptic and antidepressant drugs

It has earlier been proposed by the author that the aetiology of schizophrenic symptomatology may be due to the presence of abnormally connected interhemispheric fibres which link specialised functions in the brains of schizophrenics that are not connected in normal subjects, and that the neuroleptic drugs may produce their action through a local anaesthetic-like effect in suppression of conduction in these fibres. This line of thought has been extended here to consider the possible mechanism of action of the neuroleptic drugs in more detail, as well as that of the tricyclic antidepressant drugs which are derivatives of the phenothiazine group. Pharmacological similarities with the local anaesthetics both structurally and functionally have been considered, as well as the effects that these drug groups may have in common with the lithium salts. It has been suggested that these drugs all produce their primary effect on cell membranes, though not necessarily at the synapse, that the time course of their clinical effect may correlate with their incorporation into various cell membranes within the CNS, and that they may thus bring about a fundamental alteration in cell membrane microstructure. The possible role of electroconvulsive therapy has also been considered. The corollary of this argument is that the affective disorders may be genetically determined diseases of cell membrane microstructure.     

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Early multiple organ dysfunction syndrome appears to be facilitated with bacterial translocation in severely burn injury, yet the mechanisms of bacterial translocation remains in dispute. The aim of this study was to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation following burns and the effects of bifidobacterial supplement on gut barrier. Methods: Wistar rats were randomly divided into burn group (Burn, n=60),sham burn group (SB, n=10) in experiment Ⅰ , and burn + saline group (BS, n=30), burn + bifidobacteria group (BB, n=30), and sham-burn + saline group (SS, n= 10) in experiment Ⅱ. Animals in BB group were fed bifidobacterial preparation (5 × 109 CFU/ml) after burns, 1.5ml,twice daily. Animals in BS and SS were fed saline. Samples were taken on days 1, 3, and 5 in burn groups, and on day 3 in sham-burn groups. The incidence of bacteria/endotoxin translocation and counts of Bifidobacterium, Fungi and Escherichia coli in gut mucosa were determined with standard methods. The levels of sIgA in mucus of small intestine were measured by RIA. The positive sIgA expression in lamina propria and ileum mucosal injury was evaluated light microscopically by blinded examiners. Results: Our results showed that the incidence of bacterial translocation was increased after burns, which was accompanied by significant decrease in number of bifidobacteria but significant increase in E. coli and fungi in gut mucosa, and elevation of levels of plasma endotoxin and IL-6 (P<0. 001).The incidence of bacterial translocation was markedly reduced after 3- and 5-day supplementation of bifidobacteria compared with control group (P<0.05). The counts of mucosal bifidobacteria were increased by 4- to 40-fold,while E. coli and fungi were decreased by 2- to 30-fold and 10- to 150-fold, respectively, after bifidobacterial supplementation in contrast to control group. The damage of mucosa tended to be less pronounced after 3-day bifidobacteria-supplemented formula compared with control group [grade 2(0-6) vs. grade 4(3-6), P<0.05]. Moreover, the expression and release of sIgA was markedly augmented after 3-day bifidobacteria-supplementation formula and it returned to normal range on day 5. Conclusion: The decrease in counts and proportion of bifidobacteria in mucous membrane flora may play an important role in the development of bacteria/endotoxin translocation following thermal injury. The supplement of exogenous bifidobacteria could per se improve gut barriers, and attenuate bacteria/endotoxin translocation secondary to major burns.     

PLACENTAL CALCIUM PUMP: CLINICAL-BASED EVIDENCE

Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death. In this study we describe for the first time a case of placental calcification in a living fetus. The fetus of a normal 21-year-old pregnant woman showed heart abnormalities but the genetic analysis showed a normal male karyotype. The histology of the placenta demonstrated multiple intravillous linear and granular calcific incrustations The hemtoxylin/eosin stain of the sections revealed basement membrane calcific incrustations and intravillous calcium deposits. We postulate that the fetal circulation in the villi was impaired and the calcium that reached the villi from the mother was deposited at this level.     

人钠/二羧酸协同转运蛋白3基因调控肾小管上皮细胞线粒体膜电位的研究

目的 观察人钠／二羧酸协同转运蛋白3(hNaDC3，)对人肾脏近曲小管上皮细胞(HKC)线粒体膜电位的变化及其对细胞能量代谢的影响。方法 应用亚克隆技术构建正义pcDNA3-hNaDC3和反义pcDNA3-AhNaDC3两个真核表达载体，通过脂质体LipofectAMINE将pcDNA3-hNaDC3及pcDNA3-AhNaDC3转染至HKC细胞。克隆筛选后，用RT—PCR、Northern印迹及Western印迹鉴定外源基因的整合和表达。荧光探针JC-1观察各细胞系线粒体膜电位的变化。结果 外源hNaDC3基因稳定整合到HKC细胞基因组中，并获得高、低表达。转染正义hNaDC3cDNA的HKC细胞线粒体膜电位降低，JC-1在线粒体内形成单体，发出绿色荧光；而转染反义hNaDC3cDNA的HKC细胞线粒体膜电位略微升高，JC-1形成聚合体，发出红色荧光。结论 hNaDC3过表达引起线粒体膜电位降低，反义hNaDC3则使线粒体膜电位略微升高。提示NaDC3可能通过使线粒体膜电位下降，参与了细胞能量代谢。