Home blood sampling for plasma glucose assay in control of diabetes

Estimation of plasma glucose in home blood samples is needed to improve diabetic control. Sufficiently precise measurements on capillary blood were obtained by (a) storing Reflotest glucose-oxidase strips in a desiccant container before reading and (b) collecting blood samples into a simple vacuum bottle containing potassium fluoride (assay of sodium content indicating volume of plasma collected). The precision of the methods (+/- 1 SD) was +/-0.35 mmol/1 (+/-6.3 mg/100 ml). Clinical reliability was assessed by measuring the basal plasma glucose concentration at home on different mornings in patients with maturity-onset diabetes, the day-to-day variation (+/- 1 SD) being +/-0.73 and +/-0.92 mmol/1 (+/-13.2 and +/-16.6 mg/100 ml) respectively. The mean basal plasma glucose concentration in all 84 patients with maturity-onset diabetes from three general practices was 8 mmol/1 (144 mg/100 ml), 44 of the values exceeding 6 mmol/1 (108 mg/100 ml). Improving control by monitoring the basal plasma glucose concentration in maturity-onset diabetes might help to prevent diabetic complications.     

Do peroxisome proliferation receptor-gamma antagonists have clinical potential as combined antiobesity and antidiabetic drugs?

There is genetic evidence that reducing the activity of peroxisome proliferation receptor-gamma (PPAR-gamma) may increase insulin sensitivity. SR-202 is a selective antagonist at PPAR-gamma, which inhibits the adipocyte differentiation normally seen with the PPAR-gamma agonist rosiglitazone. SR-202 also reduces the ability of young mice to put on weight and accumulate fat. The levels of circulating TNF-alpha correlates with body fat stores and/or hyperinsulinaemia. SR-202- treated wild-type mice have reduced TNF-alpha levels. When wild-type mice are fed a high-fat diet, the plasma levels of TNF-alpha are raised, and SR-202 treatment protects against this rise. Feeding mice with a high-fat diet induced insulin resistance measured as increased plasma levels of glucose, insulin and free fatty acids, and SR-202 protected against these changes. The ob/ob mouse is diabetic at 8 weeks and plasma glucose and insulin levels continue to rise over the next 3 weeks, and treatment with SR-202 prevents these increases. The development of PPAR-gamma antagonists should continue as the results to date suggest that they have clinical potential for the treatment of diabetes Type 2 and obesity.     

Current status of viral gene therapy for brain tumours

There is genetic evidence that reducing the activity of peroxisome proliferation receptor-γ (PPAR-γ) may increase insulin sensitivity. SR-202 is a selective antagonist at PPAR-γ, which inhibits the adipocyte differentiation normally seen with the PPAR-γ agonist rosiglitazone. SR-202 also reduces the ability of young mice to put on weight and accumulate fat. The levels of circulating TNF-α correlates with body fat stores and/or hyperinsulinaemia. SR-202- treated wild-type mice have reduced TNF-α levels. When wild-type mice are fed a high-fat diet, the plasma levels of TNF-α are raised, and SR-202 treatment protects against this rise. Feeding mice with a high-fat diet induced insulin resistance measured as increased plasma levels of glucose, insulin and free fatty acids, and SR-202 protected against these changes. The ob/ob mouse is diabetic at 8 weeks and plasma glucose and insulin levels continue to rise over the next 3 weeks, and treatment with SR-202 prevents these increases. The development of PPAR-γ antagonists should continue as the results to date suggest that they have clinical potential for the treatment of diabetes Type 2 and obesity.     

Mechanistic population modeling of diabetes disease progression in Goto-Kakizaki rat muscle

Pyruvate dehydrogenase kinase 4 (PDK4) is a lipid status responsive gene involved in muscle fuel selection. Evidence is mounting in support of the therapeutic potential of PDK4 inhibitors to treat diabetes. Factors that regulate PDK4 mRNA expression include plasma corticosterone, insulin and free fatty acids. The objective was to determine the impact of those plasma factors on PDK4 mRNA and to develop and validate a population mathematical model to differentiate aging, diet and disease effects on muscle PDK4 expression. The Goto-Kakizaki (GK) rat, a polygenic non-obese model of type 2 diabetes, was used as the diabetic animal model. Muscle PDK4 mRNA expression was examined by real-time QRTPCR. Groups of GK rats along with controls fed with either a normal or high fat diet were killed at 4, 8, 12, 16 and 20 weeks of age. Plasma corticosterone, insulin and free fatty acids were measured. The proposed mechanism-based model successfully described the age, disease and diet effects and the relative contribution of these plasma regulators on PDK4 mRNA expression. Muscle growth reduced the PDK4 mRNA production rate by 14% per gram increase. The high fat diet increased the initial production rate constant in GK rats by 2.19-fold. The model indicated that corticosterone had a moderate effect and PDK4 was more sensitive to free fatty acid than insulin fluxes, which was in good agreement with the literature data.     

低碳水化合物饮食结合利拉鲁肽治疗2型糖尿病合并肥胖症的临床疗效

目的 探讨低碳水化合物饮食结合利拉鲁肽治疗2型糖尿病合并肥胖症的临床疗效.方法 将入组的60例2型糖尿病合并肥胖症患者随机分为2组,A组给予低碳水化合物饮食+利拉鲁肽干预治疗;B组给予低碳水化合物饮食,比较治疗后两组患者的体重、体重指数(BMI)、腰围、血脂(TC、TG、LDL、HDL)、脂肪率、内脏脂肪、空腹血糖(FBG)、餐后2小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)等指标的变化情况.结果 A组治疗后体重降至(79.00±11.95) kg,腰围降至(97.48±10.78) cm,BMI降至(27.72±3.10) kg/m2,TC、TG、LDL分别降至[(4.42±0.86)、(1.57±0.54)、(3.12±0.61)mmol/L],FBG、2hPBG分别为[(5.42±0.86)、(7.26±0.84)mmol/L],HbA1c降至(5.93±0.63)％,FINS为(13.72±4.20)μIU/nl;B组治疗后体重降至(81.04±8.78)kg,腰围降至(99.32±8.08) cm,BMI降至(28.84±2.35) kg/m2,TC、TG、LDL分别降至[(4.74±0.72)、(1.72±1.09)、(3.25±0.84) mmol/L],FBG、2hPBG分别为[(5.84±0.79)、(7.99±1.04) mmol/L],HbAIc降至(6.11±0.87)％,FINS为(15.71±3.27)μIU/ml,A、B组两组治疗后比较,体重、BMI、腰围、TC、TG、LDL、脂肪率、内脏脂肪FBC、2hPBG、HbA1c、FINS、HOMA-IR比较差异有统计学意义(P＜0.05),但HDL干预后改善不显著(P＞0.05).结论 低碳水化合物饮食结合利拉鲁肽可明显降低患者体重,改善肥胖相关指标、降低血糖、改善胰岛素抵抗,且效果优于单纯低碳水化合物饮食.     

Effects of energy restriction on norepinephrine turnover and serum glucose and fatty acids in lean mice

Norepinephrine (NE) turnover rate was determined in several tissues of 5-week-old female mice fed a high carbohydrate diet (58% of energy as carbohydrate, 30% fat) either ad lib or restricted to 34 or 24 kJ/day (36 to 50% restriction) presented as 1 or 2 daily meals. When the restricted intakes were divided into 2 equal meals, daily NE turnover did not differ from that of ad lib-fed mice. When the above restricted amounts were provided as a single daily meal at the beginning of the dark period, NE turnover was 38% and 46% lower, respectively, in the heart only compared to ad lib-fed controls. Serum glucose and total free fatty acids were affected by dietary conditions known to produce sympathetic activation (high carbohydrate and high fat diets) and suppression (high protein diet and energy restriction as a single meal), but the changes were unrelated to fractional NE turnover. Thus, the lower NE turnover seen when food intake is restricted is due to the prolonged overnight fast and not due to the lower energy intake per se, and is not associated with serum concentration of glucose or total free fatty acids.     

原钒酸钠对Ⅱ型糖尿病的降糖作用研究

目的　观察原钒酸钠对Ⅱ型糖尿病大鼠的降糖作用。方法　用高脂饲料灌胃正常大鼠 ,引起肥胖 ,测定血中游离脂肪酸浓度。同时应用正糖钳技术检测胰岛素抗性 ,对产生胰岛素抵抗的大鼠腹腔注射小剂量链脲菌素 (5 5mg·kg-1) ,然后筛选空腹血糖值大于 11 1mmol·L-1大鼠为糖尿病模型组。连续灌胃原钒酸钠 7d后 ,测定空腹血糖值。结果　①大鼠喂食高脂饲料后 ,正糖钳实验中维持血糖稳态所需胰岛素量增多 ,为 (0 5 4± 0 0 2 )U·min-1,高于正常组 (P <0 0 1) ;同时血中游离脂肪酸浓度增加 ,从正常 (0 4 6 9±0 0 4 7)mmol·L-1至 (1 5 32± 0 2 91)mmol·L-1(P <0 0 1) ;②原钒酸钠对正常大鼠的血糖值无影响 ,而对Ⅱ型糖尿病大鼠的空腹血糖值及糖耐量曲线下面积有降低作用 (P <0 0 5 )。结论　实验结果证明了原钒酸钠可以明显降低Ⅱ型糖尿病大鼠的空腹血糖值 ,并且对糖耐量具有保护作用     

Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents.

1. Twenty-two maturity-onset type diabetics treated with oral hypoglycaemic agents entered a single-blind crossover study using placebo (periods A and C, 2 months each) and clofibrate (2 g/day; period B; 2 months). 2. In thirteen patients, under reasonably good control, clofibrate did not reduce fasting or post-prandial blood glucose, nor 24 h glycosuria; no improvement was noted in the M-value, an index of diabetes control. 3. In contrast, in nine patients, with poor diabetes control, clofibrate reduced 24 h glycosuria and significantly improved the M-value. 4. In all patients, clofibrate therapy was associated with a significant 19-23% reduction in plasma fibrinogen. 5. It is suggested that addition of clofibrate may be useful in maturity-onset diabetics not adequately controlled by diet combined with oral hypoglycaemic agents.     

Eugenosedin‐A prevents hyperglycaemia,hyperlipidaemia and lipid peroxidation in C57BL/6J mice fed a high‐fat diet

Objectives Eugenosedin‐A is a serotonin (5‐hydroxytryptamine; 5‐HT) 5‐HT_{1b /2a} and _α1/α2/β1‐adrenoceptor blocker with anti‐oxidative, anti‐inflammatory and free‐radical scavenging activities. Previous reports demonstrated that 5‐HT_2a blockers could diminish hyperlipidaemia. This study therefore aimed to investigate the possible uses and mechanisms of eugenosedin‐A and other agents in treating hyperlipidaemia. Methods C57BL/6J mice were randomly divided into seven groups, fed a regular diet or a high‐fat diet alone or supplemented with one of five agents: eugenosedin‐A, ketanserin, prazosin, propranolol or atorvastatin (5 mg/kg p.o.) for 8 weeks. Key findings Compared with the regular diet, the mice fed the high‐fat diet had significantly higher body weight and glucose, insulin and lipid levels. Brain malondialdehyde concentration was increased and liver glutathione peroxidase activity decreased. Addition of eugenosedin‐A to the high‐fat diet resulted in less weight gain and reduced hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. Lipid and glucose homeostasis were related to decreased hepatic lipogenesis mRNAs and proteins (sterol regulatory element binding protein 1a, fatty acid synthase, sterol‐CoA desaturase) and restored adipose peroxisome proliferator‐activated receptor γ expression. Eugenosedin‐A also enhanced low‐density lipoprotein receptor mRNA expression. Conclusions Eugenosedin‐A may improve plasma lipid metabolism by increasing low‐density lipoprotein receptor and peroxisome proliferator‐activated receptor γ expression and diminishing sterol regulatory element binding protein 1a, fatty acid synthase and sterol‐CoA desaturase. Reduction of plasma glucose and lipid levels may, in turn, reduce insulin concentration, which would explain the marked improvement in obesity‐related hyperglycaemia and hyperlipidaemia. Furthermore, eugenosedin‐A affected malondialdehyde concentration and glutathione peroxidase activity, suggesting it may have anti‐peroxidation effects in mice fed a high‐fat diet.     

五味子油对2型糖尿病胰岛素抵抗大鼠的作用及机制

目的探讨五味子油对2型糖尿病大鼠胰岛素抵抗的作用及其机制。方法高脂饲料联合小剂量链脲佐菌素(STZ)诱导建立2型糖尿病大鼠胰岛素抵抗模型。将SD大鼠随机分为正常组,模型组,五味子油高剂量(1mg/kg)、低剂量(0.5 mg/kg)组,罗格列酮组。连续灌胃6周,测定空腹血糖(FBG)、空腹胰岛素(FINS)、游离脂肪酸(FFA)、血清中瘦素的水平,并计算胰岛素抵抗指数(HOMA-IR)。结果五味子油可降低FBG、FINS、FFA的水平,抑制瘦素的表达,降低HOMA-IR。结论五味子油改善2型糖尿病大鼠胰岛素抵抗的作用可能与瘦素有关。     

Regulation of glycogen metabolism by anti-dyslipidemic action of gemfibrozil and cholestyramine in a dyslipidemic-diabetic hamster model

Dyslipidemia with diabetes in hamsters, as a result of feeding with high-fat diet, caused accumulation of nonesterified fatty acid, increased lipolysis, and hyperglycemia, with decreased insulin activity. The lipid-lowering drug gemfibrozil improved insulin secretion and lowered the plasma glucose, plasma and tissue lipids viz., cholesterol, triglyceride, nonesterified fatty acids, and glycerol. Cholestyramine, a potent bile acid sequestrant was less effective than gemfibrozil in the diabetic-dyslipidemic hamster model. Treatment with the above drugs also affected glycogen metabolism by reactivation of the enzymes glycogen synthase, glucokinase, hexokinase, and glycogen phosphorylase, in liver and muscle, and reduced fat load by increasing faecal excretion of lipids. These drugs counteracted the insulin resistance by improving insulin secretion. Gemfibrozil was more effective than cholestyramine in controlling hyperglycemia, because the lipid-lowering action of the latter was mediated only by its bile acid sequestration activity.     

Effect of different intravenous nutrients on metabolic changes in short-term fasted man

It is well documented (1-3) that a balanced use of nutritive solutions is important to maintain metabolic homeostasis and a better control of nutrient flux in fasting patients. In this trial, 10 healthy males, aged 30-50 years, fasted for 12 h, were subjected to intravenous nutrient loads in three separate trials. In the first trial they received only a fat emulsion, in the second fat emulsion and L-amino acid solution, and in the third fat emulsion, L-amino acid solution and glucose solution, 240 and 480 min after intravenous infusion plasma triglycerides, serum cholesterol, free fatty acids, lactate, glucose and plasma amino acids were determined. Significant biochemical changes were detected with regard to triglycerides, lactic acid, free fatty acids, alanine, glutamine, lysine and proline concentrations, depending on the different mixtures utilized.     

益气养阴清热液对高血糖肥胖大鼠胰岛素抵抗的影响

目的观察益气养阴清热液(YYQ)对高血糖肥胖大鼠胰岛素抵抗的改善作用。方法采用高脂饲料加小剂量链脲佐菌素(STZ)诱导高血糖肥胖大鼠胰岛素抵抗,用YYQ治疗4wk。检测空腹血糖(FBG)、葡萄糖耐量(OGT)、血清胰岛素(INS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、游离脂肪酸(FFA)、红细胞膜胰岛素受体(INSR)、胰岛素钳夹实验下的葡萄糖输注率(GIR);测定肾周、附睾周围脂肪垫重量。同时测定YYQ对肝组织中IR-1、IRS-1mRNA表达的影响。结果YYQ治疗4wk后,大鼠血清中TC、TG、LDL-C、INS、FFA降低,OGT改善,而血清中HDL-C和GIR明显升高,INSR高、低亲和力受体数目均明显增多,肝组织中IR、IRS-1mRNA表达升高,各项指标均与模型组大鼠差异有显著性。结论YYQ对高血糖肥胖大鼠胰岛素抵抗有治疗作用,通过增加胰岛素受体数目而提高其胰岛素敏感性可能是其作用机制之一。     

Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats

1. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of type II diabetes with accompanying dyslipidaemia and obesity. 2. To define chromosomal intervals associated with obesity (abdominal fat weight and plasma leptin levels), dyslipidaemia (plasma triglyceride, cholesterol and free fatty acids) and hyperglycaemia (plasma glucose levels), we have performed genome-wide quantitative traits loci (QTL) analyses of 115 male OLETF x (OLETF x Fischer 344) backcross animals at 16 weeks of age. 3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306). 4. No other loci produced significant linkage to these observed phenotypes. 5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later. Thus, alterations at the Dmo1 locus are a major risk factor for pathogenesis in the strain, a finding that agrees with physiological studies that indicate a role for dyslipidaemia in the type II diabetic syndrome of OLETF rats.     

NO-1886 inhibits size of adipocytes, suppresses plasma levels of tumor necrosis factor-alpha and free fatty acids, improves glucose metabolism in high-fat/high-sucrose-fed miniature pigs.

The synthetic compound NO-1886 is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides and elevating high-density lipoprotein cholesterol. Recently, we found that NO-1886 also had a plasma glucose-reducing action in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on the morphology of adipocytes, plasma levels of tumor necrosis factor-alpha (TNF-alpha) and free fatty acids (FFA) in miniature pigs fed a high-fat/high-sucrose diet. Our results showed that feeding a high-fat/high-sucrose diet to miniature pigs increased the size of adipocytes, and the plasma levels of TNF-alpha, FFA, and glucose. This diet also induced insulin resistance and impaired the acute insulin response to glucose loading. Supplementing 1% NO-1886 to the high-fat/high-sucrose diet inhibited adipocyte enlargement, and suppressed plasma levels of TNF-alpha, FFA, and glucose. The decrease in plasma TNF-alpha and FFA was simultaneous with the decrease in plasma glucose. We also found an increased whole body glucose clearance and an increased acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 improves the glucose metabolism in high-fat/high-sucrose diet-induced diabetic minipigs by decreasing fat deposit, and suppressing plasma TNF-alpha and FFA levels. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistant syndrome.     

Long‐term Administration of Rapamycin Reduces Adiposity,but Impairs Glucose Tolerance in High‐Fat Diet‐fed KK/HlJ Mice

Abstract: Rapamycin is an immunosuppressant drug used to prevent organ rejection in transplant patients. In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high‐fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin‐treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin‐treated animals showed a marked decline in glucose tolerance as judged by the 180‐min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet‐induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance.     

Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake.

In order to investigate the effect of carbohydrate intake on ethanol-induced lipid peroxidation and cytotoxicity, rats were maintained on four different test diets, a medium-carbohydrate (carbohydrate intake, 8.4 g/day/rat on average), a low-carbohydrate (carbohydrate intake, 2.8 g/day/rat on average), an ethanol-containing medium-carbohydrate (carbohydrate and an ethanol intake, 8.4 and 2.9 g/day/rat on average, respectively), and an ethanol-containing low-carbohydrate diet (2.8 and 2.9 g/day/rat on average, respectively). Ethanol and the low-carbohydrate diet each increased the liver malondialdehyde content, but the combined effect of both (ethanol-containing low-carbohydrate diet) was much more prominent than either alone. The degree of increase in malondialdehyde content almost paralleled the activity of the microsomal ethanol oxidizing system. Both the low-carbohydrate and the ethanol-containing low-carbohydrate diets decreased the liver glutathione content, but ethanol combined with the medium-carbohydrate diet had no effect on the content. Ethanol treatment increased the liver triglyceride content only when combined with the low-carbohydrate diet. The rate of NADPH-dependent microsomal malondialdehyde formation was much higher in microsomes from rats maintained on the ethanol-containing low-carbohydrate diet than in those from rats on the ethanol-containing medium-carbohydrate diet, indicating that lowered carbohydrate intake augments ethanol-induced malondialdehyde accumulation in the liver by enhancing the rate of lipid peroxidation. In addition, when incubated with red blood cells in the presence of NADPH, microsomes from rats fed the ethanol-containing low-carbohydrate diet caused marked hemolysis, which was prevented by the addition of 5 mM glutathione to the incubation system. Furthermore, addition of 50 mM ethanol to the reaction system greatly accentuated the hemolysis. These results suggest that lowered carbohydrate intake at the time of ethanol consumption potentiates ethanol cytotoxicity by enhancing ethanol-induced lipid peroxidation.     

High-carbohydrate diets and insulin-dependent diabetics.

A high-carbohydrate-(HC)-modified fat diet was compared with a standard low-carbohydrate (LC) diabetic diet in 11 insulin-dependent diabetics. Basal and preprandial plasma glucose concentrations were appreciably lower when the patients received the HC diet derived chiefly from readily available cereal and vegetable sources (mean (+/- SE of mean) basal concentrations 6.7 +/- 1.2 mmol/l (121 +/- 22 mg/100 ml) with the LC diet and 4.3 +/- 0.7 mmol/l (77 +/- 13 mg/100 ml) with the HC diet; mean preprandial concentrations 11.1 +/- 1.2 mmol/l (200 +/- 22 mg/100 ml) LC diet and 8.9 +/- 1.3 mmol/l (160 +/- 23 mg/100 ml) HC diet). total and low-density lipoprotein cholesterol concentrations were lower when patients took the HC diet (mean 4.4 +/- 0.2 and 2.4 +/- 0.2 mmol/l (189 +/- 8 and 124 +/- 8 mg/100 ml) respectively), and the ratio of high-density lipoprotein cholesterol to total cholesterol tended to rise. The average percentage of glycosylated haemoglobin did not differ between the two diets. Thus several measures of carbohydrate and lipid metabolism appear to be more satisfactory when patients receive a HC diet, which is an acceptable alternative to that still recommended to most insulin-requiring patients.     

Lipogenic action of cycloheximide on the rat epididymal fat pad

Cycloheximide produced a 10-fold increase in the incorporation of glucose into lipids of the rat epididymal fat pad and a 43 per cent decrease in plasma free fatty acids. These changes were observed 2hr after the intraperitoneal injection of 1 mg/kg of the antibiotic to male rats fasted for 16–20hr and weighing between 120 and 170 g. Under the same conditions, subcutaneous adipose tissue showed a 2-fold increase, while brain, liver and brown adipose tissue did not give any response. The 10-fold increase was absent in fed rats and was lower (4-fold) in male animals weighing over 250 g and in 120–170 g female rats when the parametrial adipose tissue was studied. The higher incorporation of glucose into lipids produced by Cycloheximide was also smaller in the epididymal fat pad from orchiectomized (2-fold), adrenalectomized (3-fold) and alloxan diabetic (7-fold) rats. Hormonal substitutive treatment with testosterone in orchiectomized animals and with cortisol, corticosterone or epinephrine in adrenalectomized animals did not elicit the response obtained in intact rats. The relative distribution of the label from radioactive glucose into lipid extracts between glycerol and fatty acids after Cycloheximide treatment resembles that found in control rats, but differs from that observed after insulin administration. Actinomycin-D, chloramphenicol and puromycin did not mimic the action of cycloheximide on lipid metabolism. Epididymal fat pads obtained from fasted male rats injected 1 hr earlier with Cycloheximide showed, after 60 min of incubation, a 5-fold increase in the incorporation of glucose into lipids, a 37 per cent increase in the release of glycerol and a 36 per cent diminution in the release of free fatty acids into the incubation mixture, when compared to the values obtained with the tissues of the control animals. It is postulated that in the rat epididymal fat pad Cycloheximide has a marked lipogenic effect together with an accelerated fatty acid re-esterification which is independent of both insulin secretion and inhibition of protein synthesis.     

红杉醇对2型糖尿病大鼠脂代谢的影响

目的:观察红杉醇对2型糖尿病大鼠脂代谢的影响.方法:采用高糖高脂饮食加腹腔注射小剂量链脲佐菌素(Streptozotocin,STZ)诱导2型糖尿病大鼠模型35只,灌服红杉醇(50、25及12.5 mg·kg-1· d-1)6周,每天1次.全自动生化分析仪测定血清TG、TC、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)含量;ELISA法检测血浆游离脂肪酸(Free fatty acids,FFA)、肝脏载脂蛋白A1(Apolipoprotein A1,Apo-A1)和载脂蛋白B1(Apolipoprotein B1,Apo-B1)含量;放射免疫法测定肝组织瘦素(Leptin)含量;MASSON染色观察肝脏病理改变.结果:红杉醇能显著降低模型大鼠血脂、FFA含量,下调肝组织Apo-B1及Leptin水平,上调肝组织Apo-A1的含量,减轻肝细胞脂肪变性,减少肝细胞间质和血管旁胶原沉积.结论:红杉醇具有调节2型糖尿病大鼠脂代谢、减轻脂肪肝和肝脏胶原沉积的作用.