Carbohydrate metabolism in uremia

Abnormalities of insulin and glucose metabolism, namely glucose intolerance, inhibition of insulin secretion and insulin resistance, are present in children with chronic renal failure. Insulin resistance is universal among children with end-stage renal disease and may be caused by uremic toxins accumulated because of reduced renal function. The normal response of the beta cell is to enhance insulin secretion to overcome the insulin resistance. In patients with secondary hyperparathyroidism, this increase in insulin secretion is inhibited, resulting in glucose intolerance. Presence of glucose intolerance may be responsive for the growth retardation in uremic children. Improvements in glucose tolerance correlate with improvements in linear growth in uremic children. Further research should be directed towards investigation of the mechanisms by which abnormal energy utilization may affect growth in uremia and development of indices of glucose metabolism as predictors of growth in aremia.     

Intermediary metabolism

Carbohydrate and fat form the immediate and long-term energy stores of the body. Protein constitutes the active (functional) cell mass and is also an energy source but, normally, a relatively minor one. All three macronutrients are interrelated. Proteins are synthesized from amino acids derived from ingested protein. Glucose and fat provide energy via adenosine triphosphate. The brain and red blood cells can only obtain their energy from glucose. Glucose is oxidized via the glycolytic and the tricarboxylic acid (Krebs) cycle pathways. Fatty acids are metabolized by the process of β-oxidation, whereby two carbon fragments are cleaved from the fatty acid chain and enter the Krebs cycle. Amino acids are deaminated to keto acids and the nitrogen moiety excreted in the urine mostly as urea. The keto acids enter the metabolic pathways at various points, mostly in the Krebs cycle. Glucose can be synthesized from lactate, glycerol and amino acids (gluconeogenesis), but not from fatty acids.     

Intermediary metabolism

Carbohydrate and fat form the immediate and long-term energy stores of the body. Protein constitutes the active (functional) cell mass and is also an energy source but, normally, a relatively minor one. All three macronutrients are interrelated. Proteins are synthesized from amino acids derived from ingested protein. Glucose and fat provide energy via adenosine triphosphate. The brain and red blood cells can only obtain their energy from glucose. Glucose is oxidized via the glycolytic and the tricarboxylic acid (Krebs) cycle pathways. Fatty acids are metabolized by the process of β-oxidation, whereby two carbon fragments are cleaved from the fatty acid chain and enter the Krebs cycle. Amino acids are deaminated to keto acids and the nitrogen moiety excreted in the urine mostly as urea. The keto acids enter the metabolic pathways at various points, mostly in the Krebs cycle. Glucose can be synthesized from lactate, glycerol and amino acids (gluconeogenesis), but not from fatty acids.     

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

Intermediary metabolism

Intermediary metabolism refers to the sum of all intracellular chemical processes by which nutritive material is converted into cellular components. It includes anabolism (synthesis of macromolecules) and catabolism (breakdown of macromolecules). Cellular energy is generated from aerobic oxidation of metabolic fuels (carbohydrates, fats, proteins) derived from digestion of a meal or from breakdown of internal stores. These metabolic fuels are broken down into basic substrates (glucose, amino acids, free fatty acids, glycerol). This is followed by processes that remove electrons (oxidation) from these substrates at high potential and transfer them to substrates at lower potential. It is during these processes that energy is released. Reduced coenzymes (NAD⁺ and FADH) are intermediate energy storage compounds that aid electron (and energy) transfer from metabolic reactions (glycolysis and Krebs cycle) to the electron transport chain. In the electron transport chain, electrons are transferred through a series of carriers of lower potential and energy released during this is used to form adenosine triphosphate. These electrons finally combine with the end electron acceptor oxygen, to form water. During aerobic metabolism, oxygen is consumed at the end of electron transport chain producing carbon dioxide via Krebs cycle. However, energy can also be generated anaerobically via glycolysis with the production of lactate.     

静脉皮瓣糖代谢的实验研究

我们在兔胸腹部以胸腹壁静脉为轴,形成静脉皮瓣、无血供回植皮瓣及轴型皮瓣。通过对皮瓣组织中乳酸脱氢酶同功酶的测定,探讨静脉皮瓣移植后的糖代谢变化规律。静脉皮瓣移植后24 h 内,皮瓣内保留的氧合血红蛋白可维持皮瓣正常的糖代谢。此后糖的有氧氧化水平缓慢下降,并维持在一定水平。术后72 h 皮瓣内糖的有氧氧化水平最低,术后4天开始增强,术后7天恢复正常。     

静脉皮瓣糖代谢的实验研究

我们在兔胸腹部以胸腹壁静脉为轴，形成静脉皮瓣、无血供回植皮瓣及轴型皮瓣。通过对皮瓣组织中乳酸脱氢酶同功酶的测定，探讨静脉皮瓣移植后的糖代谢变化规律。静脉皮瓣移植后２４ｈ内，皮瓣内保留的氧合血红蛋白可维持皮瓣正常的糖代谢。此后糖的有氧氧化水平缓慢下降，并维持在一定水平。术后７２ｈ皮瓣内糖的有氧氧化水平最低，术后４天开始增强，术后７天恢复正常。     

Sterility of Three Brothers in Connection with a Disturbed Carbohydrate Metabolism in Semen

Sterile semen of three brothers was investigated biochemically. Most strikingly was the strong similarity of both the amino acid and the carbohydrate composition of the semen. Inside the spermatozoa much more fructose and glucose was present than normally is found. It could be shown that in the seminal plasma peptides and proteins were present all containing more or less beta-alanine and all able to bind glucose and fructose. After incubation with labelled glucose it was evident that inside the spermatozoa enzymes requried for formation of lactic acid were lacking or inactive. Moreover labelled tyrosine and serine was found. Treatment with proviron did not improve carbohydrate metabolism but the amounts of present glucose and fructose inside the spermatozoa had strongly decreased. It is supposed that the sterility of the men is due to a disturbance in spermatogenesis.     

胃旁路术对糖尿病大鼠糖脂代谢的影响

目的 观察Roux-en-Y胃旁路术对糖尿病Coto-Kakizaki(CK)大鼠糖脂代谢的影响.方法 18只GK大鼠随机等分为Roux-en-Y胃旁路手术组(RYGB组)、假RYGB组和对照组;观察手术后1、2、4、12周各组大鼠空腹血糖、C肽和体质量增加值变化,同时观察手术后4周、12周血浆糖化血红蛋白、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量变化.结果 手术前3组大鼠各检测指标差异无统计学意义(P>0.05).手术后1、2、4、12周RYGB组大鼠空腹血糖(7.0±0.8比6.5±1.0比6.3±1.5比5.6±1.7比4.3±0.5,P<0.01)明显降低,空腹C肽(0.21±0.06比0.28±0.09比0.52±0.06比0.71±0.06比0.78±0.06,P<0.01)显著升高;手术后4、12周大鼠糖化血红蛋白(9.71±1.34比9.09±1.21比7.34±1.17,P<0.01)、甘油三酯(1.32±0.17比0.87±0.05比1.22±0.15,P<0.01)、低密度脂蛋白胆固醇(1.61±0.25比1.21±0.20比1.16±0.15,P<0.01)明显降低,高密度脂蛋白胆同醇(0.83±0.10比1.11±0.12比1.23±0.16,P<0.01)明显升高(P<0.01).各组大鼠体质量增加值差异均有统计学意义(P<0.05).假RYGB组和对照组其余各检测指标的变化差异均无统计学意义(P>0.05).结论 Roux-en-Y胃旁路术可改善非肥胖糖尿病GK大鼠血糖和血脂代谢,且与体质量变化无关.     

PPARγ对前列腺癌细胞增殖及糖酵解的影响

目的:研究PPAR-γ基因表达对前列腺癌细胞增殖和肿瘤特殊糖酵解代谢的影响。方法:采用RNAi技术构建PPARγ低表达的腺病毒载体并转染到前列腺癌细胞株,并以空白载体为对照组,进行细胞增殖检测、细胞凋亡检测、糖酵解代谢基因及产物乳酸检测,并比较两组之间的结果差异。结果:经RNAi抑制的PPAR-γ前列腺癌细胞株与对照组相比,蛋白表达量降低至(26.00±4.06)%,增殖抑制率最大为第2天达(39.50±4.92)%,细胞凋亡率升高至(21.03±3.08)%,糖酵解代谢基因产物(Myc和Glut-1)下降,第4天培养液中乳酸浓度为对照组的69.71%,上述结果具有统计学差异(P<0.01)。结论:抑制PPAR-γ基因的表达有望成为治疗前列腺癌新方法。     

Effect of cyclosporin A on carbohydrate metabolism in the rat

Liver and kidney carbohydrate metabolism was investigated in rats treated with daily doses of 15 mg/kg body weight cyclosporin A (CyA) for 2 and 8 weeks or of 50 mg/kg body weight CyA for 2 weeks. The higher dosage caused significantly reduced liver glycogen and liver glycogen synthetase activity (of both active I-form and total enzyme activity), whereas the activity of the glycogen-degrading enzyme phosphorylase (active a-form and total activity) remained unchanged. Plasma glucose and glucagon levels, as well as blood ketone bodies of these animals, increased significantly and plasma insulin decreased. In contrast, kidney glycogen and glucose content were higher in rats treated with 50 mg CyA, probably due to enhanced ketone body utilization. Reduced liver glycogen synthetase activity was also found in rats treated with 15 mg CyA. Our data suggest that hypoinsulinemia, induced by CyA, might be a contributing factor to the hyperglycemia, which is mainly due to inhibition of liver glycogen synthesis. This article is dedicated to Professor Dr. August Heidland, Chief of the Division of Nephrology, University of Würzburg, FRG, on the occasion of his 60th birthday     

围手术期患者能量代谢研究进展

围手术期由于术前禁食、手术刺激、术中低温、术后疼痛不适、能量物质缺乏等原因,引起应激代谢反应,表现为胰岛素抵抗、分解代谢增强、合成代谢抑制,不利于患者恢复.此文对应激代谢反应可能的机制以及改善围手术期能量代谢的方法进行综述.     

破骨细胞能量代谢的研究进展

破骨细胞在骨代谢中发挥重要的噬骨功能,其分化成熟和功能发挥对骨代谢具有重要意义.破骨细胞分化和发挥功能阶段都需要能量代谢的参与,能量代谢的异常会导致破骨细胞分化功能的异常,从而导致骨代谢的异常.本文拟从能量代谢的角度综述破骨细胞分化和发挥功能的不同阶段,其主要的能量来源和调控机制.     

Cerebral Energy State and Glycolytic Metabolism During Enflurane Anesthesia in the Rat

The effects of enflurane anesthesia on the cerebral cortical energy state and glycolytic metabolism were studied in rats. Twenty-four rats were divided into four groups with increasing concentrations of enflurane in the arterial blood, i.e. control (1,9±0.3 mg/dl, means+s.e.mean), level I (16.1 ±1.1 mg/dl), level II (26.0± 1.6 mg/dl), and level III (32.9±0.9 mg/dl). At level I, high voltage 1–3 Hz slow waves superimposed on low voltage 10–12 Hz waves were predominant, and at levels II and III, spiking activity and burst suppression were recorded in the EEG. The duration of suppression at level III was significantly longer than that at level II. During enflurane anesthesia, there were no significant differences compared with the control group in the cerebral energy state or energy charge. Glycolytic metabolism remained unchanged except for an increase in glucose at levels II and III. Effects of hypocapnia and hypercapnia were examined in an additional 12 rats with an enflurane concentration in the blood similar to that al level II. Irrespective of PacOz levels, there were no significant changes in cerebral energy charge and glycolytic metabolites except for a decrease in glucose and an increase in lactate at hypocapnia. It was concluded that there was neither evidence of derangement of energy state nor increased anaerobic metabolism in the cerebral cortex during enflurane anesthesia.     

Effect of Exercise on Disorders of Carbohydrate and Lipid Metabolism in Adults With Traumatic Spinal Cord Injury: Systematic Review of the Evidence

Background/Objective:

Carbohydrate and lipid metabolism disorders may affect adults with spinal cord injuries (SCIs) differently than able-bodied individuals because of reduced physical activity in the SCI population. The objective of this study was to conduct a systematic review to determine the effectiveness of exercise to improve carbohydrate and lipid metabolism disorders in adults with chronic SCI.

Methods:

Studies were identified in MEDLINE (1996–2008), Cochrane Library, bibliographies of identified articles, and expert recommendations. English language articles were included if they evaluated adults with chronic SCI; evaluated exercise; and reported carbohydrate-, lipid-, and/or cardiovascular disease-related outcomes.

Results:

Twenty-two studies met inclusion criteria, including 15 intervention case-series and 7 cross-sectional surveys using self-reported physical activity measures. Intervention protocols involved active (n  =  7) or electrically stimulated (n  =  7) exercise or an educational program (n  =  1) from 8 to 52 weeks in duration. Frequency of exercise was typically 2 to 3 sessions/week, lasting 30 to 60 minutes/session. Totals of 150 and 369 subjects participated in studies with carbohydrate (n  =  12) or lipid and cardiovascular (n  =  16) outcomes, respectively; 78% were men. Level of SCI ranged from C4 to L5 and included both incomplete and complete lesions. Outcomes measures included fasting and postload blood glucose and insulin concentrations and serum cholesterol levels. Small sample sizes and variations in study design, intervention, SCI characteristics, and reported outcomes precluded quantitative pooling of results or reliable assessment of metabolic efficacy. No intervention studies assessed cardiovascular outcomes.

Conclusions:

Evidence is insufficient to determine whether exercise improves carbohydrate and lipid metabolism disorders among adults with SCI. Expert consensus, based on the preliminary evidence, is needed to inform future studies.     

成骨细胞能量代谢的研究进展

骨骼作为脊椎动物机体运动和支撑的组织器官,对维持机体正常生理功能具有重要的意义.骨骼的生长、矿化和重塑过程都离不开能量代谢.成骨细胞在骨代谢平衡中发挥重要的作用.本文拟从能量代谢的角度综述在骨重塑过程中成骨细胞主要的能量来源和调控机制.     

术前口服碳水化合物改善术后胰岛素抵抗的作用及其机理研究

目的评价机体对口服碳水化合物的耐受性、观察口服碳水化合物对术后胰岛素抵抗的作用并探讨其可能机理。方法选取择期行结直肠癌根治术患者32例并随机分为对照组和试验组。对照组术前禁食，试验组术前口服碳水化合物溶液。分别比较2组患者术前主观舒适度、术前以及术后即刻HOMA指数，术后即刻2组间PTK活性，P13K、PKB和GluT4的mRNA和（或）蛋白表达水平。结果试验组临手术前口渴感、饥饿感和焦虑感较对照组明显改善（P〈0．05）；与术前比较，术后试验组胰岛素敏感指数降低了33％，而对照组降低了38％（P=0．0072）；术后试验组PTK活性、PKB及P13K的mRNA和蛋白表达水平均高于对照组（P〈0．05，P〈0．01），但2组的GluT4 mRNA表达水平比较差异无统计学意义（P〉0．05）。结论术前口服碳水化合物安全有效，它可改善术后即刻的胰岛素抵抗。这种富糖溶液可在麻醉或手术开始时就通过相对增强胰岛素信号转导通路上PTK、P13K、PKB等激酶的活性来增强胰岛素活性，这是术前口服碳水化合物改善术后胰岛素抵抗的可能机理之一。     

Relationship of deranged energy metabolism in liver and kidney to arterial ketone body ratio following liver ischemia in rats

Changes in energy metabolism in the liver and kidney in liver ischemia induced in rats were simultaneously studied, in terms of energy charge (EC) and mitochondrial oxidoreduction state. Mean arterial blood pressure, glucose and lactate, total ketone bodies (acetoacetate+β-hydroxybutyrate) and the ketone body ratio in arterial blood (KBR) were also investigated. During and after liver ischemia, both organs showed similar patterns of reversibility, and KBR, which reflects the mitochondrial oxidoreduction state, correlated well with EC, in both organs. Referring to the mortality and changes in substrates above mentioned, KBR is a pertinent parameter for detection of viability following induced liver ischemia. It was also suggested that KBR may indicate a regulation role by the liver, in kidney energy metabolism.     

Roux-en-Y胃肠道重建改善非肥胖性糖尿病胃癌患者的糖脂代谢

目的 观察Roux-en-Y胃肠道重建对非肥胖件糖尿病胃癌患者血糖和血脂代谢的影响.方法 非肥胖性糖尿病胃癌患者57例行根治性远端胃切除术,其中35例行Roux-en-Y胃肠道重建,22例行Billroth Ⅰ式胃肠道重建.观察手术前、手术后3个月和6个月两组体质量指数、糖化血红蛋白、空腹血糖、胰岛素、C肽、甘油三酯、总胆固醇、高密度脂蛋白和低密度脂蛋白含量的变化,并检测口服葡萄糖后2 h血糖、胰岛素和C肽的变化.结果 手术前两组各检测指标之间相比差异均无统计学意义(P＞0.05).手术后两组体质量指数变化之间相比差异无统计学意义(P＞0.05);术前、手术后3个月和6个月Roux-en-Y胃肠道重建组空腹血糖为(9.3±0.9)mmol/L比(7.2±2.1)mmoL/L比(7.1±0.8)mmoL/L,P=0.000;糖化血红蛋白为(9.2±1.2)%比(7.3±1.2)%比(7.2±1.1)%,P=0.000;空腹甘油三酯为(3.21±0.88)mmoL/L比(2.12±0.97)mmol/L比(2.02±0.09)mmol/L,P=0.000;空腹总胆固醇为(6.4±1.9)mmol/L比(4.3±1.0)mmol/L比(4.1±1.0)mmol/L,P=0.000;空腹低密度脂蛋白为(3,61±1.05)mmol/L比(2.77±0.68)mmol/L比(2.71±0.18)mmol/L,P=0.000;2 h血糖为(17.6±2.5)mmoL/L比(12.1±1.9)mmoL/L比(11.6±2.3)mmol/L,P=0.000,含量较手术前明显下降(P＜0.01).空腹胰岛素为(98±11)pmol/L比(120±9)pmoL/L比(122±8)pmol/L,P=0.000;空腹C肽为(0.21±0.08)mmol/L比(0.30±0.01)mmol/L比(0.30±0.01)mmol/L,P=0.000;空腹高密度脂蛋白为(1.08±0.10)mmol/L比(1.61±0.34)mmol/L比(1.62±0.09)mmol/L,P=0.000;2 h胰岛素为(410±19)pmol/L比(446±19)pmol/L比(459±18)pmol/L,P=0.000;2 h C肽为(0.87±0.17)mmol/L比(1.22±0.14)mmol/L比(1.19±0.15)mmol/L,P=0.000.Billroth Ⅰ式胃肠道重建组糖化血红蛋白为(9.2±1.2)%比(8.4±1.6)%比(8.3±1.1)%,P=0.046.结论 Roux-en-Y胃肠道重建术可改善非肥胖性糖尿病胃癌患者血糖和血脂代谢,且与体质量指数变化无关.