L-Cysteine Increases Glucose Uptake in Mouse Soleus Muscle and SH-SY5Y Cells

Previous investigation demonstrated the potential of L-cysteine (L-Cys) at high concentrations to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake and quantity of glucose transporters (GLUTs 3 and 4) in mouse soleus muscle and C2C12 muscle cells, as well as in human SH-SY5Y neuroblastoma cells, were investigated. A marked enhancement of glucose uptake was demonstrated, peaking at 5.0 mM L-Cys in soleus muscle (P < 0.05) and SH-SY5Y cells (P < 0.001), respectively. In contrast, glucose uptake was not affected in the C2C12 muscle cells. Kinetic analysis of the SH-SY5Y glucose uptake showed a 2.5-fold increase in maximum transport velocity compared with controls (P < 0.001). In addition, both GLUT3 and GLUT4 levels were increased following exposure to L-Cys. Our findings point to a possible hypoglycemic effect of L-Cys.     

口服糖耐量试验中血糖和胰岛素动态变化对瘦素的影响

目的　利用口服葡萄糖耐量试验（ＯＧＴＴ）中体内血糖和胰岛素浓度的改变,探讨血糖和胰岛素对瘦素可能存在的即时和短时效应。方法　５０ 例Ⅱ型糖尿病和５０ 例非糖尿病个体（ 年龄、性别和体重指数相匹配）做ＯＧＴＴ,测定０、３０、６０、１２０、１８０ 分钟时相的血浆葡萄糖、血清胰岛素和瘦素水平。结果　糖尿病组空腹血清瘦素水平男性为（３．８８ ±０．６４） μｇ／Ｌ,女性为（８．３０ ±１．０６） μｇ／Ｌ ;非糖尿病组男性为（５ ．０１ ±０．６４） μｇ／Ｌ,女性为（１０．４８±１．３０） μｇ／Ｌ ,两组差别无显著性。与非糖尿病组相比,糖尿病组ＯＧＴＴ血糖升高明显,而胰岛素释放曲线呈反应低平,高峰不明显或延迟相。瘦素释放曲线两组均呈下降趋势,糖尿病组这种趋势更为明显。结论　血瘦素水平未曾随着胰岛素浓度的升高而升高,相反表现为昼夜节律性的下降,提示胰岛素促瘦素分泌的效应相对较弱,未能影响瘦素白天下降的趋势。     

High prevalence of obesity among nursing personnel working in tertiary care hospital

Aim

To find out the prevalence of obesity and glucose intolerance among nurses working in tertiary care hospital.

Increased lipid synthesis by liver slice in a superfusion system following raised glucose or insulin concentration

Summary The synthesis of lipid from¹⁴C-glucose and³H-alanine was measured from rat liver slices using a micro-superfusion technique that allows continuous monitoring of the perifusate output. Increase in substrate glucose results in prompt elevation of fatty acid synthesis. Insulin addition also produced an increased¹⁴C incorporation into lipid. The effects were independent. Both these factors may be active in the hypertriglyceridaemia of high carbohydrate intake or diabetes.

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Erhöhte Lipidsynthese von Leberschnitten in einem Superfusionssystem nach erhöhten Konzentrationen von Glucose und Insulin

Zusammenfassung An Rattenleberschnitten wurde mit einer Mikrosuperfusionstechnik, die eine dauernde Kontrolle des Perfusatflusses erlaubt, die Lipidsynthese aus¹⁴C-G-lucose und³H-Alanin gemessen. Eine Erhöhung des Glucosesubstrats führte zu einer sofortigen Steigerung der Fettsäuresynthese. Zugegebenes Insulin erzeugte ebenfalls einen erhöhten¹⁴C-Einbau in die Lipide. Beide Effekte waren unabhängig. — Diese beiden Faktoren können in der Hypertriglycerinämie nach hoher Kohlenhydrataufnahme oder beim Diabetes wirksam sein.

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Augmentation de la synthèse des lipides par des coupes de foie dans un système de superfusion après élévation de la concentration de glucose ou d'insuline

Résumé La synthèse des lipides à partir du¹⁴C-glucose et de la³H-alanine fut mesurée dans des tranches de foie de rat, en utilisant une technique de microsuperfusion qui permettait l'enregistrement continu du débit du périfusat. L'addition de glucose amena une hausse immédiate de la synthèse d'acide gras. L'addition d'insuline provoqua de même une augmentation de l'incorporation de¹⁴C dans les lipides. Les effets étaient indépendants. Ces deux facteurs pourraient être actifs dans l'hypertriglycéridémie après l'absorption importante d'hydrates de carbone ou dans l'état diabétique.

     

辛伐他汀对老年急性冠状动脉综合征患者hsC和sICAM-1及预后的影响

目的:研究辛伐他汀对急性冠状动脉综合征(ACS)患者外周血清可溶性细胞间黏附分子-1(sICAM-1)、超敏C反应蛋白(hsC)和心血管事件预后的影响。方法:将73例经冠状动脉造影证实的ACS患者随机分为对照组35例和治疗组38例。对照组给予控制血压、降糖、抗凝、抗血小板及改善心肌供血等治疗,调脂药物采用血脂康治疗,治疗组在此基础上加用辛伐他汀20 mg。治疗前及治疗3周后,分别测定血总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、sICAM-1及hsC,观察2组患者出院后6个月内因不稳定型心绞痛再住院、急性心肌梗死、血运重建及死亡等MACE事件发生情况。结果:辛伐他汀治疗组TC、LDL-C、hsC、sICAM-1水平降低(P<0.05);6个月内的不良心脏事件(MACE)显著减少。结论:辛伐他汀可显著减少老年ACS患者MACE的发生率,降低血hsC、sICAM-1水平,改善预后。     

How to Design a Biosensor

Amperometric sensors for continuous glucose monitoring could prevent acute and chronic complications of diabetes, but research is needed to improve accuracy and stability. In designing sensors, interference from non-glucose analytes can be minimized by use of filtration membranes or electron transfer mediators that allow polarization at low potentials. If oxygen is required for the enzymatic reaction with glucose, then the outer permselective membrane must have substantial oxygen permeability. For this reason, during development of permselective membranes, permeability studies (such as performed by Tipnis and colleagues in this issue) can be used to measure transport of glucose and oxygen and optimize membrane structure. Tipnis and colleagues present a novel biosensor based with separate layers for glucose-oxygen permselectivity, enzymatic conversion, and avoidance of interference. They also address sensor stability, in part by comparing sensor function during ascending vs descending glucose levels. By measuring the difference, they were able to minimize this aspect of instability (hysterisis), which assisted them in selecting a promising permselective membrane based on iron and humic acid.     

Aldolase C/zebrin gene regulation by prolactin during pregnancy and lactation

Prolactin (PRL) is necessary for the genesis of mammary alveolar buds and for lactation. A cDNA library enriched for PRL-dependent genes was made by suppression subtractive hybridization. Aldolase C/zebrin (AldC/zebrin), a “brain-specific” aldolase, was found to be PRL-dependent in the mouse mammary glands. AldC/zebrin was preferentially expressed in the alveolar buds. Expression of the gene in the ovary was also evident. During pregnancy, mammary AldC/zebrin mRNA levels were elevated beginning at midpregnancy (d 10 of pregnancy) in accordance with the genesis of the lobuloalveolar system, and the expression level was gradually increased through the end of pregnancy. Lactating mammary gland contained a very high level of AldC/zebrin mRNA, and the gene expression decreased during involution. By contrast, levels of aldolase A and B mRNA expression in the mammary glands were less affected by pregnancy and lactation. The selective regulation of AldC/zebrin may contribute to a shift in nutrient metabolism during pregnancy and lactation to facilitate epithelial growth and biosynthesis of milk constituents.     

Determination of peritoneal glucose kinetics in rats: implications for the peritoneal implantation of closed-loop insulin delivery systems

Summary Peritoneal glucose kinetics were evaluated in the anaesthetized rat, to assess whether the peritoneal cavity would be a suitable site for the implantation of membrane-protected islets of Langerhans (bioartificial pancreas) or the glucose sensor of an artificial B cell. Glucose was measured in peritoneal fluid samples aspirated by needle puncture. Basal peritoneal and blood glucose concentrations were identical in 16 h fasted (n=4) and non fasted (n=3) animals. After 10 min of an i.v. glucose infusion (n=15) the increment in peritoneal glucose concentration was 63±3% of the increment in blood glucose concentration and both values were significantly correlated (r=0.92; p<0.001). After 10 min of glucose clamping (12.6±0.8 mmol/l), the increment in peritoneal glucose concentration was 69±3% (n=5; p<0.05) of the increment in blood glucose concentration. In three additional experiments it was 93±3% of the increment in blood glucose concentration (NS), after 30 min of glucose clamping (8.0±0.5 mmol/l). Peritoneal glucose concentration monitored by a glucose sensor: (a) followed blood glucose sluggishly during a glucose clamp (n=5), confirming the data shown above, (b) followed blood glucose with a 5 min delay and reached the same plateau after the intravenous injection of 1U insulin (n=3; NS). We conclude that peritoneal glucose reflects blood glucose at basal state and during variations of glycaemia, nevertheless, presenting heterogeneous kinetics. These kinetics might be appropriate for a bioartificial pancreas but not for an in vivo calibration procedure, of a peritoneally implanted glucose sensor.     

The effect of verapamil on myocardial exchange of free fatty acids, citrate, lactate and glucose in coronary artery disease

Twelve patients with coronary artery stenosis (> 50% diameterreduction) underwent two identical periods of atrial pacingbefore and after i. v. verapamil (0.1 mg/kg). Myocardial exchangesof free fatty acids (FFA), citrate, lactate and glucose wereevaluated from measurements of arterio-coronary sinus differences(n = 12) and coronary sinus blood flow (CSBF) (n = 9). Beforeverapamil 11 patients developed angina. Verapamil abolishedpain in seven and improved pacing time to angina in four patients.After verapamil, aortic pressure decreased (P < 0.05), whilethe rate pressure product remained unchanged during rest andpacing. Verapamil decreased CSBF by 20% (P<0.05) during pacing,and increased oxygen extraction both during pacing and recovery.During pacing verapamil increased net FFA extraction (P<0.01)and uptake (1 to 8 µmol/min P<0.05), and decreasedglucose extraction (P<0.05) and uptake (22 to 11 µmol/min P< 0.02. Verapamil increased myocardial citrate releaseduring pacing (P < 0.05), suggesting a citrate inhibitionof glycolysis as a possible mechanism of the inhibited glucoseuptake. During pacing, verapamil reduced lactate release inseven patients (P<0.05) and decreased lactate extractionin five patients (P<0.05). The results suggest that verapamilmediates its beneficial effect on pacing-induced angina, inpart by changing substrate utilization of the ischaemic myocardiumin man towards that of normal heart.     

Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study

Aims/hypothesis Both insulin resistance and beta-cell dysfunction play a role in the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM) through impaired glucose tolerance (IGT). The aim of the study was to define the level of glycaemia at which beta-cell dysfunction becomes evident in the context of existing insulin resistance.Methods Insulin response (OGTT) and insulin sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects the insulin secretion/insulin resistance index (I/G÷IR) was calculated as the ratio of the increment in plasma insulin to the increment in plasma glucose during the OGTT divided by insulin resistance, as measured during the clamp.Results In lean NGTs with a 2-h plasma glucose concentration (2-h PG) between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive decline in I/G÷IR compared with NGTs with a 2-h PG less than 5.6 mmol/l. There was a further decline in I/G÷IR in IGTs with a 2-h PG between 7.8 and 9.3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed coincident patterns of relation of 2-h PG to I/G÷IR.Conclusion/interpreation When the plasma insulin response to oral glucose is related to the glycaemic stimulus and severity of insulin resistance, there is a progressive decline in beta-cell function that begins in normal glucose tolerant individuals.Abbreviations T2DM, Type 2 diabetes mellitus - FPG, fasting plasma glucose - 2-h PG, 2-h plasma glucose - EGP, endogenous glucose production - Ra, rate of appearance - TGD, total glucose disposal - IR, insulin resistance