Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.     

高糖通过活化半胱氨酸天冬氨酸蛋白酶3途径诱导人腹膜间皮细胞凋亡

目的 探讨高糖损伤人腹膜间皮细胞(HPMC)的机制。方法 (1)分离培养HPMC,以细胞形态、免疫细胞化学染色作细胞鉴定;(2)第2代HPMC分别经含1.5%、2.5%、4.25%葡萄糖的M199培养基培养48h后(以正常M199培养基和含4.25%甘露醇的M199培养基为对照),检测HPMC caspase-3活性和HPMC凋亡情况;(3)分别用25μmol/L、50μmol/L、和100μmol/LZ-VAD.fmk和4.25%葡萄糖共同刺激体外培养的HPMC(以DMSO和4.25%葡萄糖为对照),流式细胞仪观察HPMC凋亡情况,同时检测50μmol/L Z-VAD.fmk组和葡萄糖对照组caspase-3活性。结果 (1)HPMC caspase-3活性和凋亡率与葡萄糖浓度呈正相关(r分别为0.9506和0.9868,P<0.01),且HPMC caspase-3活性与凋亡率呈正相关(r=0.9860,P<0.01)。与M199对照组相比,2.5%葡萄糖组和4.25%葡萄糖组HPMC caspase-3活性和凋亡率显著增加(P<0.05),而1.5%葡萄糖组及4.25%甘露醇组HPMC caspase-3活性和凋亡率无显著差异(P>0.05)。(2)4.25%葡萄糖组caspase-3活性显著高于4.25%甘露醇组(P<0.05),但4.25%甘露醇组caspase-3活性与对照组相比无显著差异(P>0.05)。(3)与对照组相比,Z-VAD,fmk组HPMC凋亡率(P<0.05)和caspase-3活性(P<0.05)显著下降,且HPMC凋亡率与Z-VAD.fmk呈负相关(r=-0.8836,P<0.01)。结论 (1)高糖能以     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.     

高血糖对急性颅脑伤预后的影响

对ＩＣＵ收治的６１例急性闭合性颅脑伤患者入院２４ｈ血糖水平与急性期格拉斯哥昏迷评分、颅脑伤不同类型及预后进行分析。结果提示：格拉斯哥昏迷评分与血糖水平经回归分析呈显著负相关（ｒ＝－０．９６４，Ｐ＜０．０１）；不同类型颅脑伤患者以脑挫裂伤组血糖最高。高血糖组患者病死率明显高于非高血糖组，死亡组患者血糖明显高于恢复不良组及恢复良好组。作者认为，血糖测定有助于了解颅脑伤的严重程度，同时可以估计患者的预后，在颅脑伤的救治过程中加强血糖监测是必要的。     

Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.     

Relationship between maternal glycaemia and birth weight in glucose-tolerant women from different ethnic groups in New Zealand.

AIM: The aim of this study was to compare the population attributable fraction(PAF) for a large baby (> or =4 kg) due to glycaemia, weight and smoking in glucose-tolerant women from different ethnic groups. METHODS: A retrospective review of screening for gestational diabetes (GDM)and associated birth weight was undertaken in New Zealand European (n= 529), Maori (n= 540) and Pacific (n= 916) women. The proportion with a large baby was compared by 1-h post 50-g glucose challenge test tertile and maternal weight tertile. RESULTS: Large babies were more common from Pacific and European than Maori women (24.3%, 18.8%, 8.9%, respectively; P<0.001). Birth weight increased significantly with increasing glucose among Pacific women (P<0.001) even after adjusting for maternal weight and other confounders. The risk of having a large baby was 2.56 (1.82-3.60)-fold greater in women in the highest maternal weight tertile (> or =84 kg), with a significantly greater PAF in Pacific women(27.2%, 12.9%, 16.4%, respectively; P<0.001). The odds ratio (OR) of having a large baby increased with even mildly elevated maternal 1-h glucose concentrations [OR for 5.6-6.2 mmol/l: 1.54 (1.11-2.14); for > or =6.3 mmol/l: 2.06 (1.50-2.82)], with no ethnic differences in PAF (11.1-11.8%, 16.7-18.7%, respectively). Smoking and being Maori were associated with smaller babies. CONCLUSIONS: Increased maternal weight and glycaemia are associated with a greater proportion of large babies among glucose-tolerant women. Growth of Pacific babies may be more sensitive to a higher maternal glucose when the mother is obese.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

琼脂糖凝胶电泳法测定糖化血红蛋白及其临床应用

目的　采用琼脂糖凝胶电泳的方法测定糖化血红蛋白 (Hb Alc) ,了解 Hb Alc与空腹血糖的关系。方法　取正常人及糖尿病人 EDTA- K2抗凝全血 2 32例 ,制成血红蛋白溶液 ,使用法国 sebia公司 sebia HYDRASYS电泳仪及光密度计扫描仪 ,用琼脂糖凝胶进行电泳分离和光密度计扫描定量测定 Hb Alc;在全自动生化分析仪上用己糖激酶法测定空腹血糖。结果　对照组的 Hb Alc平均值 (% )为 x± s=5 .4 1± 0 .94 ,血糖的平均值 (mmol/ L )为 x± s=4 .92± 0 .87;糖尿病人的 Hb Alc平均值 (% )为 x± s=11.0 6± 4 .3,血糖的平均值 (mmol/ L )为 x± s=10 .86± 3.0 4 ,P<0 .0 1,血糖值与Hb Alc值有显著相关性 ,r=0 .985 ,回归方程 Y=1.10 15 x 1.815。结论　该方法标本用量少 ,分辨率高 ,重复性好 ,结果不受温度及胎儿血红蛋白的影响 ,Hb Alc可作为糖尿病控制的指标     

Nocturnal hypoglycaemia in Type 1 diabetic patients,assessed with continuous glucose monitoring: frequency,duration and associations

Aims We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple‐injection therapy (MIT) using a continuous subcutaneous glucose sensor. Methods A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA_1c 7.8 ± 0.9%) and 33 patients on MIT (HbA_1c 8.7 ± 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA_1c, diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Results Nocturnal hypoglycaemia ≤ 3.9 mmol/l occurred in 33.3% of both the CSII‐ (8/24) and MIT‐treated patients (11/33). Mean (± sd ; median, interquartile range) duration of hypoglycaemia ≤ 3.9 mmol/l was 78 (± 76; 57, 23–120) min per night for the CSII‐ and 98 (± 80; 81, 32–158) min per night for the MIT‐treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Conclusions Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.