Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats

We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content.     

合理使用高张葡萄糖

临床护理工作中发现，高张葡萄糖的使用，在某些情况下存在一定的危险性，使用不当则加重病情的发展，甚至危及病人的生命。因此要掌握好高张葡萄糖对某些疾病所产生的不良影响，做到预防在先，合理使用。     

Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.     

Effects of glucagon-like peptide 1 (7–36 amide) on whole-body protein metabolism in healthy man

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-¹³C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P  < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP-1 administration ( P  < 0.0005). Plasma insulin increased after 3 h of GLP-1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline ( P  < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.     

THE EFFECT OF SOME α2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

1. The effects of graded doses of the α₂-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the α₂-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.     

肝硬化患者胰岛素释放试验的临床意义

本文报道46例肝硬化患者口服葡萄糖胰岛素释放试验的结果,并与18名正常人和18名原发性糖尿病患者比较。肝硬化患者糖耐量减低者28例(60.9％),其中29例(43.5％)呈糖尿病型耐量曲线。胰岛素释放高峰值在服糖后2h;释放过多和分泌延迟者32例(69.6％),降低者4例(8.7％)。20例肝源性糖尿病患者的胰岛素释放指数明显高于原发性糖尿患者。笔者认为血浆胰岛素和胰岛素释放指数测定对鉴别这两种类型的糖尿病有很大价值。     

仙人掌提取物对小鼠血糖的影响

目的 :探讨仙人掌水性和酸性提取物对小鼠血糖的影响。方法 :糖尿病小鼠造模成功后分为 5组 :仙人掌酸提物 2个剂量组 (0 .5g·kg-1·d-1和 1.0g·kg-1·d-1) ,水提物 2个剂量组和优降糖组 (2 0 0mg·kg-1·d-1)。正常小鼠灌注等量生理盐水作为正常对照。 6组小鼠均连续给药 2 1d后测血糖。结果 :给药后仙人掌酸提物 2个剂量组血糖均较给药前降低 (P均 <0 .0 5 ) ,2个剂量组间差异无统计学意义 (P >0 .0 5 ) ,但 2组与优降糖组相比 ,P均 <0 .0 5 ;水提物 2个剂量组给药前后血糖无明显变化 (P >0 .0 5 )。结论 :仙人掌酸提物有降血糖作用     

Peri-operative liver graft function: monitoring using the relationship between blood glucose and oxygen consumption during anaesthesia

The purpose of our study was to test the hypothesis that the quotient between plasma glucose and whole body oxygen consumption (VO2) as a 'metabolic index' is a sensitive indicator of early graft function. Arterial levels of glucose and oxygen consumption were determined in 100 consecutive patients during orthotopic liver transplantation performed without anhepatic veno-venous bypass. Patients were divided into survivors with no obvious problems related to graft function and those with primary nonfunction of the graft. The neohepatic increase in VO2 was significantly higher in survivors (112 +/- 4 vs 88 +/- 11 ml.min-1.m-2; p < 0.05), whereas blood glucose levels after reperfusion were higher (352 +/- 18 vs. 287 +/- 36 mg dl-1) in those with primary non-function of the graft. The calculated metabolic index was also higher (4.02 +/- 0.93 vs 2.67 +/- 0.45, p < 0.05) in patients with primary nonfunction of the graft. Our principal conclusion was that 92% of normal functioning liver grafts could be classified correctly by the metabolic index immediately after reperfusion, whereas glucose levels and VO2 alone classified only 67% and 70% of normal functioning liver grafts correctly.     

Physiological Effects of Mental Stress and Orthostasis in Young Insulin-Dependent Diabetic Patients

ABSTRACT. The effects of procedures which stimulate sympathetic activity, viz. mental stress induced by a colour-word conflict test (CWT) for 20 min, and orthostasis (ORT) for 8 min were studied in 8 young (16-20 yr) insulin-dependent diabetes mellitus (IDDM) patients and 9 age and sex-matched healthy controls. The IDDM patients showed no signs of neuropathy or retinopathy and their mean HbA_1c value was 8.4 ±0.6% (normal value < 5.0 %). Blood pressure and heart rate increased significantly during CWT and ORT in both groups. The changes in systolic blood pressure and heart rate were comparable in both groups during CWT; the IDDM group showed a higher ( p < 0.05) heart rate after 8 min of orthostasis, however. CWT and ORT elicited equivalent increases in noradrenaline in venous plasma in both groups ( p < 0.05), but the IDDM patients had 50% lower values ( p < 0.01) at rest, during CWT and at rest after CWT than controls. CWT and ORT evoked equivalent plasma adrenaline increases in both groups. The lipolysis marker, plasma glycerol, was about 40 % lower ( p < 0.05) in the IDDM group before and after CWT. Yet, mental stress evoked equivalent increases in glycerol levels ( p < 0.01) in both groups. These findings indicate that sympathetic activity in the young diabetic patients without signs of neuropathy may be blunted.     

The pharmacokinetics of (125I) 3-deoxy-3-iodine glucose on experimental tumor modelsin Vivo

The dynamics of¹²⁵I distribution is studied in rats with induced tumors of the prostate and mammary gland for intravenous administration of¹²⁵I-3D-G. It is found that 80% of the activity is eliminated in the first 24 hours. A relatively high level of¹²⁵I accumulation is found in necrotically altered regions of the tumor. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, № 3, pp. 294–295, March, 1994.