Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic beta-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant alpha-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet alpha-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high alpha-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients.     

Effects of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats

We investigated the effect of magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl), a marker compound isolated from the cortex of Magnolia officinalis, in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. The rats were treated orally with magnolol (100 mg/kg body weight) once a day for 13 weeks. In magnolol-treated GK rats, fasting blood glucose and plasma insulin were significantly decreased, and the pancreatic islets also showed strong insulin antigen positivity. Urinary protein and creatinine clearance (Ccr) were significantly decreased. Pathological examination revealed the prevention of the glomeruli enlargement in magnolol-treated GK rats. The overproduction of renal sorbitol, advanced glycation endproducts (AGEs), type IV collagen, and TGF-beta1 mRNA were significantly reduced in magnolol-treated GK rats. Thus based on our findings, the use of magnolol could result in good blood glucose control and prevent or retard development of diabetic complications such as diabetic nephropathy.     

Efficiency of asbestos shading for growth of Barki rams during hot summer

Twenty-four growing Barki rams, 5–6 months old with an average body weight of 22 kg, were divided into asbestos shaded and unshaded groups during summer. Ad libitum feeding on roughage with 0.5 kg of concentrates per head per day was practiced. Drinking water was available twice daily in the early morning and afternoon. Biweekly observations included rectal temperature (RT; °C), and respiration rate (RR; breaths per minute) at 06:00 h and 14:00 h were recorded. Meteorological data, plasma glucose, calcium, inorganic phosphorus and packed cell volume were also measured. Results indicated that experimental animals developed hyperthermia during June to September, as evidenced by higher (P < 0.01) RT and RR than normal (40 ± 0.05 and 103.9 ± 3.87 vs. 38.9 ± 0.10 and 40 ± 6.56, respectively). Diurnal variations in these physiological phenomena were closely associated (P < 0.05) with ambient temperature changes. As compared with the unshaded group, providing an asbestos shed reduced (P < 0.05) RT and RR in the hyperthermic animals during the day (39.9 ± 0.07 and 94.7 ± 3.75 vs. 40.1 ± 0.08 and 113.1 ± 4.74, respectively), but it increased (P < 0.05) these parameters during summer nights (39.5 ± 0.05 and 82.4 ± 0.95 vs. 39.2 ± 0.07 and 71.6 ± 2.41, respectively). It also increased (P < 0.05) packed cell volume 1 h after morning drinking (35 ± 0.97 vs. 33.2 ± 0.60); reduced (P < 0.05) plasma glucose (43.3 ± 5.88 vs. 53.2 ± 6.31); caused hypocalcemia (10.9 ± 0.35 vs. 11.5 +- 0.43; P < 0.05) and hypophosphatemia (3.9 ±0.35 vs. 4.6 ± 0.34; P < 0.05) as a result of hyperthermia. Monthly variations in all parameters studied were higher (P < 0.01) during early summer. It is concluded that providing an asbestos shed for growing Barki rams under Egyptian summer conditions will not protect the animals from hyperthermia by day and night, as it interferes with extra body heat dissipation to the surroundings during summer nights. Although the unshaded animals were more hyperthermic during summer days, they tended to be normal during the night.     

Exercise in the heat: Effects of dinitrophenol administration

1. 1.|Dinitrophenol (DNP) was administered to rats in two equal dosages (20 mg/kg, 30 min interval); the second injection was followed immediately by exercise (9.14 m/min) in the heat (30°C) or at room temperature (21°C).

2. 2.|At 21°C control (saline-treated) rats manifested a mean endurance of 94 min which was reduced to 32 min among DNP-treated animals.

3. 3.|At 30°C, control rats ran for 65 min (δT_re/min = 0.05°C) while DNP-treated animals had a mean endurance of only 12 min (δT_re/min = 0.22°C).

4. 4.|DNP-treated rats (30°C) manifested no decrements in tail-skin heat loss (δT_sk/min = 0.17°C vs 0.10°C) or saliva secretion (0.78 g/min, DNP vs. 0.19 g/min, control) for their brief treadmill duration.

5. 5.|The increased metabolic heat production of DNP severely reduced performance.

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

Chromium supplementation improves glucose tolerance in diabetic Goto-Kakizaki rats

Chromium supplementation (Cr) may be useful in the management of diabetes and appears to improve some aspects of glucose handling. However, several studies have used either high doses of Cr supplementation or have placed control animals on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the ranges that more closely approximate recommended levels of supplementation in humans are efficacious in glycemic control under normal dietary conditions. Euglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (a model of nonobese NIDDM) were assigned to water (control) or chromium picolinate (Cr-P) supplementation (1 or 10 mg/kg/day) groups for up to 32 weeks. Glucose tolerance was tested following an overnight fast by injecting sterile glucose (1.0 g/kg, i.p.) and then measuring blood glucose at select times to determine the sensitivity to glucose by calculation of the area under the curve. Cr-P did not significantly alter the growth of the animals. In the euglycemic Wistar rats, Cr-P supplementation did not alter the response to a glucose tolerance test. In the GK rats, Cr-P supplementation significantly improved glucose tolerance at both levels of Cr-P supplementation (1 mg/kg/day: H20; 100 +/- 11%; Cr-P 70 +/- 8%; 10 mg/kg/day: H(2)0; 100 +/- 10%; Cr-P 66 +/- 9 %). Cr-P supplementation produced a small improvement in some indices of glycemic control. There were no differences observed for the two levels of Cr-P supplementation suggested that we did not identify a threshold for Cr-P effects, and future studies may use lower doses to find a threshold effect for improving glucose tolerance in diabetics.     

The effect of 4-week streptozotocin-induced diabetes on responses to endothelin-1 in rat isolated atria

The effect of endothelin-1 has been examined on isolated spontaneously beating right atria and electrically driven left atria from diabetic rats and age-matched controls. Diabetes was induced by a single i.v. injection of streptozotocin (65 mg/kg) 4–5 weeks before the experiments. Endothelin-1 (0.01–100 nM) caused concentration-dependent increases in atrial rate and force; the increases were not different between atria from diabetic and control rats. The ability of endothelin-1 to reduce chronotropic and inotropic responses to noradrenaline was also not different between the two groups. Endothelin-1 (10 nM) decreased the chronotropic response to sympathetic nerve stimulation (2 Hz, 10 s) in atria from control rats by 68 ± 5% (n = 8), but this decrease was slightly smaller (45 ± 6%, N = 8) in atria from diabetic rats.

The results provide no evidence to suggest that the diabetic state markedly alters cardiac responses to endothelin-1.     

The effects of in vivo and in vitro non-enzymatic glycosylation and glycoxidation on physico-chemical properties of haemoglobin in control and diabetic patients

The erythrocyte deformability, which is related to erythrocyte internal viscosity, was suggested to depend upon the physico-chemical properties of haemoglobin. In the present study we employed ESR spectroscopy in order to explore further the extent to which the in vivo or in vitro glycation and/or glycoxidation might affect haemoglobin structure and conformation. We revealed that under both in vivo and in vitro conditions the attachment of glucose induced a mobilization of thiol groups in the selected domains of haemoglobin molecules (the increased h₊₁/h₀ parameter of maleimide spin label, MSL; 0.377 ± 0.021 in diabetics vs 0.338 ± 0.017 in controls, n = 12, P < 0.0001). The relative rotational correlation time (τ_c) of two spin labels, TEMPONE and TEMPAMINE, respectively, in erythrocyte insides (5.22 ± 0.42 in diabetics, n = 21 vs 4.79 ± 0.38, n = 16 in controls, P < 0.005) and in the solutions of in vitro glycated haemoglobin, were increased. Neither oxidation nor crosslinking of thiol groups was evidenced in glycated and/or oxidized haemoglobin. In addition, erythrocyte deformability was found to be reduced in type 2 diabetic patients (6.71 ± 1.08, n = 28 vs 7.31 ± 0.96, n = 21, P < 0.015). In conclusion, these observations suggest that: the attachment of glucose to haemoglobin might have decreased the mobility of the Lys-adjacent Cys residues, thus leading to the increased h₊₁/h₀ parameter of MSL. Such structural changes in haemoglobin owing to non-enzymatic glycosylation may contribute to the increased viscosity of haemoglobin solutions (r = 0.497, P < 0.0035) and the enhanced internal viscosity of diabetic erythrocytes (r = 0.503, P < 0.003). We argue that such changes in haemoglobin, and consequently in red blood cells, might contribute to the handicapped oxygen release under tissue hypoxia in the diabetic state.     

Body condition and protein supplementation positively affect periovulatory ovarian activity by non LH-mediated pathways in goats

Effects of rumen undegradable intake protein (UIP) supplementation on ovarian activity and serum insulin, GH, and LH were evaluated in goats having low or high body condition (BC). Goats with either low BC (n = 16, 28.7 ± 0.8 kg BW, BC = 2.1 ± 0.3) or high BC (n = 16, 38.4 ± 0.8 kg, BC = 3.2 ± 0.3) received, during 40-days, one of the two protein supplementation levels: without UIP or with UIP (120 g goat⁻¹ d⁻¹). Oestrus was synchronized with two i.m. doses of PGF₂, and jugular blood samples were collected from 36 to 42 h after the second prostaglandin injection at 15 min intervals. Serum concentrations of insulin, LH, and GH were measured The number of preovulatory follicles and the number of corpora lutea (CL) were evaluated by transrectal ultrasonography at 1 and 4 days after the second prostaglandin dose, respectively. Does with higher BC had more CL than those in the lower condition group (2.8 ± 0.2 versus 1.8 ± 0.2, P < 0.05). Similarly, goats receiving UIP supplementation had more follicles (2.6 ± 0.2 versus 1.9 ± 0.2, P < 0.05) and tended to have more CL (2.6 ± 0.2 versus 2.0 ± 0.2, P = 0.05) than does not receiving UIP. Neither BCS nor UIP supplementation affected serum GH or LH concentrations, pulsatility, or area under the curve. High BC does produced more insulin (1.92 ± 0.17 versus 0.81 ± 0.17 ng/mL, P < 0.01 ng/mL) than lower BC goats; the same for UIP-supplemented (1.69 ± 0.18 versus 1.04 ± 0.18, P < 0.05). Results suggest that the increased ovarian activity observed in both UIP-supplemented and higher BC goats was not the result of changes in LH or GH, suggesting effects at a local level, through changes in insulin in a non-GnRH-gonadotrophin dependent manner.     

Ameliorating effect of chromium administration on hepatic glucose metabolism in streptozotocin-induced experimental diabetes

Chromium has been recognized as an essential trace element that plays an important role in carbohydrate metabolism. However, the molecular mechanisms involved in its action are not clear. This study was undertaken to understand the mechanism of chromium action in experimental diabetes. Streptozotocin-induced diabetic animals were administered chromium as chromium picolinate (CrP) at a daily dose of 1 mg/kg body weight for a period of 4 weeks. It was observed that chromium complexed with picolinate was effective in lowering plasma glucose levels as well as was able to alleviate polyphagia, polydipsia, and weight loss in diabetic animals. Administration of chromium was also found to normalize glycogen content in liver of diabetic animals to near control levels. The reduction in plasma glucose levels by chromium was accompanied by increase in activity of glycolytic enzymes (e.g., glucokinase, phosphofructokinase, and pyruvate kinase) and by suppression in activity of gluconeogenic enzymes (e.g., glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) in liver. Hepatic glucose uptake was found to be increased by chromium supplementation as demonstrated by decrease in Km and increase in Vmax values in diabetic animals. Chromium levels were lower in the liver of diabetic rats when compared with that of control rats. A negative correlation was observed between plasma glucose and chromium concentration in patients with diabetes. The data suggests that chromium supplementation as CrP is beneficial in correcting hyperglycemia, implying that the modulation of the glucose metabolism by chromium may be therapeutically beneficial in the treatment of diabetes.     

外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制

目的: 观察外源性精胺对糖尿病肾病(DN)肾纤维化的保护作用,并探讨其机制。方法: 24 只雄性 C57 小鼠随机分为正常组(Control)、糖尿病组(T1D)和精胺预处理组(T1D+Sp,每组 n=8)。一次性注射 STZ(60 mg/kg)复制 1 型糖尿病小鼠模型,精胺预处理组在 STZ 注射前两周每天腹腔注射精胺(Sp,5 mg/(kg·d)),随后隔天注射精胺,第 12 周处死小鼠,检测血清肌酐、尿素氮判断肾功能变化,HE、PAS 和 Masson 染色观察肾组织损伤和纤维化水平。Western blot 法检测小鼠肾组织中基质金属蛋白酶(MMP-2、MMP-9)、IV型胶原(Coll-IV)蛋白的表达。结果: 与 Control 相比,T1D 组血糖(5.67±0.22 vs 28.40±0.57 mmol/L)、肌酐(14.33±1.22 vs 30.67±4.73 μmol/L)、尿素氮(6.93±4.94 vs 22.00±1.04 mmol/L)明显升高(P＜0.05),肾组织基底膜增厚,胶原含量明显增加,MMP-2、MMP-9 和 Coll-IV 蛋白表达均升高(分别为 0.57±0.07 vs 1.06±0.20、47.00±0.04 vs 1.29±0.09和0.42±0.16 vs 0.95±0.18,P＜0.05),精胺预处理明显减轻上述变化。结论: 外源性精胺预处理通过调节 MMPs 与胶原的平衡减轻 DN 小鼠的肾纤维化。     

Comparison of independent and combined chronic metabolic effects of GIP and CB1 receptor blockade in high-fat fed mice

GIP receptor antagonism with (Pro³)GIP protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat diet. Furthermore, cannabinoid CB₁ receptor antagonism with AM251 reduces appetite and body weight gain in mice. The present study has examined and compared the effects of chronic daily administrations of (Pro³)GIP (25 nmol/kg body weight), AM251 (6 mg/kg body weight) and a combination of both drugs in high-fat fed mice. Daily i.p. injection of (Pro³)GIP, AM251 or combined drug administration over 22 days significantly (P < 0.05 to <0.01) decreased body weight compared with saline-treated controls. This was associated with a significant (P < 0.05 to <0.01) reduction of food intake in mice treated with AM251. Plasma glucose levels and glucose tolerance were significantly (P < 0.05) lowered by 22 days (Pro³)GIP, AM251 or combined drug treatment. These changes were accompanied by a significant (P < 0.05) improvement of insulin sensitivity in all treatment groups. In contrast, AM251 lacked effects on glucose tolerance, metabolic response to feeding and insulin sensitivity in high-fat mice when administered acutely. These data indicate that chemical blockade of GIP- or CB₁-receptor signaling using (Pro³)GIP or AM251, respectively provides an effective means of countering obesity and related abnormalities induced by consumption of high-fat energy-rich diet. AM251 lacks acute effects on glucose homeostasis and there was no evidence of a synergistic effect of combined treatment with (Pro³)GIP.     

辣木叶对糖尿病大鼠认知功能及海马神经细胞凋亡的影响*

目的:探讨辣木叶对链脲佐菌素(STZ)诱导的糖尿病模型大鼠认知功能障碍及海马神经细胞凋亡的影响。方法:选取健康SD雄性大鼠50只,随机选取10只作为对照组,40只大鼠给予腹腔注射25 mg/kg STZ构建糖尿病大鼠模型。40只大鼠随机分为模型组、辣木高、中、低剂量组,分别每日灌胃给药2.0 g/kg、4.0 g/kg、8.0 g/kg辣木叶,对照组和模型组每日灌胃给药等量生理盐水,1次/日,持续给药8周。Morris水迷宫实验评价大鼠学习记忆能力;HE染色及免疫组化染色对大鼠海马神经元切片进行染色,观察各组大鼠海马神经元病理改变的情况及Bax、caspase-3及Bcl-2蛋白表达情况;酶联免疫法(ELISA)检测大鼠海马组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)。结果:与对照组相比,模型组大鼠血糖值明显提高(P＜0.01),血胰岛素水平明显降低(P＜0.05);与模型组相比,辣木组血糖值显著降低(P＜0.05,P＜0.01),辣木中、高剂量组血胰岛素水平显著升高(P＜0.05,P＜0.01)。不同剂量组辣木组间比较,给药后3组大鼠FBG及INS无统计学差异(P＞0.05);Morris水迷宫实验的第4-5日,与模型组相比较,辣木各剂量组潜伏期均明显缩短(P＜0.05);辣木不同剂量组目标象限停留时间明显延长(P＜0.05)。炎症因子变化结果,与模型组相比较,辣木低、中、高剂量组TNF-α、IL-6含量及蛋白表达水平显著降低(P＜0.05)。HE染色及免疫组化染色结果显示,与模型组相比较,辣木中剂量组中阳性表达,呈棕黄色,细颗粒状。辣木叶中剂量组(53.21±7.19)能显著减少神经元细胞凋亡的数目(P＜0.01);辣木组中剂量组大鼠海马组织中Bax、caspase-3的蛋白表达及Bax/Bcl-2比例显著降低(P＜0.05)。结论:辣木叶能改善糖尿病大鼠认知功能障碍其作用机制可能与调节Bax、Bcl-2、caspase-3的蛋白表达,降低炎症因子TNF-α及IL-6含量相关。     

Peripheral insulin administration attenuates the increase in neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats

Fasting increases neuropeptide Y (NPY) concentrations in the arcuate nucleus (ARC), its site of synthesis, and in other regions of the rat hypothalamus. Neuropeptide Y is a potent central orexigenic agent and may therefore stimulate appetite during fasting. We tested the hypothesis that low plasma insulin levels stimulate ARC levels of NPY in fasted rats. Compared with freely fed controls (n = 8), rats fasted for 72 h (n = 8) showed significantly lower plasma insulin levels (28.9 ± 1.6 vs. 52.6 ± 5.7 pmol/l; p < 0.001) and higher ARC NPY concentrations (14.2 ± 1.8 vs. 8.4 ± 2.2 fmol/μg protein; p < 0.001). Fasted rats treated with subcutaneous insulin (5 U/kg/day; n = 10), which nearly normalized plasma insulin (46.6 ± 2.8 pmol/l), showed intermediate ARC NPY levels (11.2 ± 1.4 fmol/μg protein; p < 0.01 vs. controls and untreated fasted rats). Insulin administered peripherally, therefore, attenuates fasting-induced NPY increases in the ARC, supporting the hypothesis that hypoinsulinemia stimulates hypothalamic NPY.     

瘦素对糖尿病大鼠糖脂代谢及炎性因子的影响

目的: 探讨瘦素对糖尿病大鼠糖脂代谢及相关炎症因子的影响。方法: 将健康Wistar雄性大鼠60只随机选取10只作为对照组,50只给予高糖高脂饲料喂养加腹腔内注射链脲佐霉素(STZ,25 mg/kg)的方法诱发并建立糖尿病大鼠模型。并随机分为模型组、瘦素低剂量组、瘦素中剂量组和瘦素高剂量组,每组10只。4组大鼠造模成功后均持续给予高糖高脂饲料喂养,瘦素低、中、高剂量组给予20 μg/kg、50 μg/kg和100 μg/kg,连续5 d。GOD-PAP法检测大鼠血糖(FBG),放射免疫法测定胰岛素含量(Ins),全自动生化分析仪测定血清中三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)。采用酶联免疫方法(ELISA)测定丙二醛(MDA)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)。采用Western blot检测糖尿病大鼠脂肪组织中瘦素表达情况。结果: 与对照组比较,各组大鼠血糖水平均显著升高(P＜0.01);与模型组比较,瘦素中、高剂量大鼠血糖显著降低(P＜0.05,P＜0.01);瘦素高剂量组胰岛素水平显著降低(P＜0.01)。不同剂量瘦素组间比较,给药后三组大鼠FBG及INS无统计学差异(P＞0.05)。与模型组比较,瘦素中、高剂量组TC水平显著下降(P＜0.05,P＜0.01);高剂量组TG、LDL-C水平显著降低(P＜0.05),高剂量组HDL-C水平显著升高(P＜0.01)。不同剂量瘦素组进行组间比较,高剂量组在降低TC、TG、LDL-C水平,升高HDL-C水平优于中、低剂量组(P＜0.05)。Western blot结果显示,与模型组(52.27±10.93)比,瘦素高剂量组100 μg/kg(40.13±9.87)、中剂量组50 μg/kg(44.68±10.23)、低剂量组20 μg/kg(47.35±12.09)脂肪中瘦素表达水平依次降低。结论: 瘦素水平分泌异常是诱发糖尿病因素之一,在给予一定浓度外源性瘦素(100 μg/kg)干预下,能显著降低MDA、TNF-α水平,提高IL-6水平,其机制可能与瘦素在减轻炎症反应、氧化应激,纠正血脂异常紊乱有密切关系。     

Alpha-lipoic acid mitigates insulin resistance in Goto-Kakizaki rats.

Impaired glucose uptake and metabolism by peripheral tissues is a common feature in both type I and type II diabetes mellitus. This phenomenon was examined in the context of oxidative stress and the early events within the insulin signalling pathway using soleus muscles derived from non-obese, insulin-resistant type II diabetic Goto-Kakizaki (GK) rats, a well-known genetic rat model for human type II diabetes. Insulin-stimulated glucose transport was impaired in soleus muscle from GK rats. Oxidative and non-oxidative glucose disposal pathways represented by glucose oxidation and glycogen synthesis in soleus muscles of GK rats appear to be resistant to the action of insulin when compared to their corresponding control values. These diabetes-related abnormalities in glucose disposal were associated with a marked diminution in the insulin-mediated enhancement of protein kinase B (Akt/PKB) and insulin receptor substrate-1 (IRS-1)-associated phosphatidylinostol 3-kinase (PI 3-kinase) activities; these two kinases are key elements in the insulin signalling pathway. Moreover, heightened state of oxidative stress, as indicated by protein bound carbonyl content, was evident in soleus muscle of GK diabetic rats. Chronic administration of the hydrophobic/hydrophilic antioxidant alpha -lipoic-acid (ALA, 100 mg/kg, i.p.) partly ameliorated the diabetes-related deficit in glucose metabolism, protein oxidation as well as the activation by insulin of the various steps of the insulin signalling pathway, including the enzymes Akt/PKB and PI-3 kinase. Overall, the current investigation illuminates the concept that oxidative stress may indeed be involved in the pathogenesis of certain types of insulin resistance. It also harmonizes with the notion of including potent antioxidants such as ALA in the armamentarium of antidiabetic therapy.     

Plasma copper and lipid peroxidation in cigarette smokers

Plasma levels of copper and lipid peroxidation were evaluated in 14 smokers as compared to 14 nonsmokers. Plasma copper concentrations were higher in smokers than in nonsmokers (122.5 ± 19.15 vs. 101.5 ± 16.2 μg/dl, P < .01). Plasma lipoperoxidation, evaluated as fluorescent damage products of lipid peroxidation (FDPL), also was higher in smokers than in nonsmokers (20.35 ± 2.6 vs. 17.1 ± 2.95 units of relative fluorescence/ml, P < .01). A significant and positive correlation between the number of cigarettes smoked, expressed as pack years, and the levels of either FDPL (r = .61, P < .025) or copper (r = .55, P < .05) was found. Moreover, a significant and positive relationship between copper and FDPL values was observed in smokers (r = .64; P < .025), but not in nonsmokers. These data indicate that cigarette smoke-related plasma oxidant load may be partly due to enhanced levels of the prooxidant metal copper, potentially suggesting the supplementation of specific antioxidants (e.g., zinc) to counteract cigarette smoke-induced oxidative stress in smokers.     

表没食子儿茶素没食子酸酯对大鼠胰岛素抵抗的影响

目的研究表没食子儿茶素没食子酸酯（EGCG）对自发性2型糖尿病GK大鼠的胰岛素抵抗的影响及作用机制。方法 自发性2型糖尿病GK大鼠40只,同系健康对照Wistar大鼠10只,大鼠随机分为：正常对照组、2型糖尿病对照组、2型糖尿病低剂量EGCG（50 mg/kg）治疗组、中剂量（100 mg/kg）组、高剂量EGCG（300 mg/kg）组。干预6周后,分别检测葡萄糖耐量试验、胰岛素耐受试验、肝脏GcK、G6P以及PEPCKmRNA表达情况,以及骨骼肌细胞膜GLUT4含量的变化。结果各剂量治疗组的糖耐量均得到明显改善（P〈0.05）,胰岛素耐量在240 min时较模型对照组有明显差异（P〈0.05）。与模型组比较,低剂量和中剂量治疗组均能提高肝脏葡萄糖激酶（GcK）mRNA的表达（P〈0.05）,同时抑制葡萄糖-6-磷酸酶（G6P）和磷酸烯醇式丙酮酸激酶（PEPCK）mRNA的表达（P〈0.05）;高剂量治疗组肝脏三类酶mRNA的表达与模型对照组相比无明显差异。各剂量治疗组GK大鼠的骨骼肌细胞膜GLUT4的含量较模型对照组均具有明显上调（P〈0.05）。结论中低剂量EGCG可以改善GK大鼠胰岛素抵抗,其作用机制可能与抑制肝脏糖异生作用以及骨骼肌GLUT4的转位水平有关,并且EGCG具有代偿胰岛素的作用。     

Significant Improvement of Insulin Resistance of GK Rats by Treatment with Sodium Selenate

We studied the effect of sodium selenate on insulin resistance of Goto-Kakizaki (GK) rats. Rats were kept on standard laboratory chow with and without i.p. injections of sodium selenate (0.173 mg/kg body weight) for 14 days, and then subjected to the glucose clamp. The glucose clamp studies confirmed an improvement in insulin-stimulated glucose disposal in GK rats treated with sodium selenate, with respect to both insulin sensitivity and responsiveness. This amelioration of insulin resistance may be partly due to a direct effect of the sodium selenate on peripheral tissues. 2-Deoxyglucose uptake in sodium selenate-treated adipocytes was increased and the insulin findings suggest that sodium selenate increases not only insulin sensitivity but also insulin responsiveness. Sodium selenate also accelerated glucose incorporation into adipocytes of rats, suggesting that the action of sodium selenate is peripheral. Interestingly, sodium selenate at a high concentration (about 1 mmol/L) was more effective than insulin in enhancing glucose uptake. The present study suggested that sodium selenate treatment led to substantial improvement in peripheral insulin resistance.     

Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve insulin sensitivity in fructose-rich chow-fed rats.

Ginsenoside Rh2, one of the ginsenosides contained in the Panax ginseng root, was employed to screen the effect on insulin resistance of rats induced by a diet containing 60% fructose. Single intravenous injection of ginsenoside Rh2 decreased the plasma glucose concentrations in 60 minutes in a dose-dependent manner from 0.1 mg/kg to 1 mg/kg in rats with insulin resistance induced by fructose-rich chow. Repeated intravenous injection of ginsenoside Rh2 (1 mg/kg per injection, 3 times daily) into rats which received fructose-rich chow for 3 consecutive days decreased the value of glucose-insulin index, the product of the areas under the curve of glucose and insulin during the intraperitoneal (i.p.) glucose tolerance test. This means that ginsenoside Rh2 has an ability to improve insulin action on glucose disposal. The plasma glucose lowering action of tolbutamide, induced by the secretion of endogenous insulin, is widely used to characterize the formation of insulin resistance. Time for the loss of plasma glucose lowering response to tolbutamide (10 mg/kg, i.p.) in rats during insulin resistance induction by fructose-rich chow was also markedly delayed by the repeated treatment of ginsenoside Rh2, as compared to the vehicle-treated control. Thus, the repeated treatment of ginsenoside Rh2 delayed the development of insulin resistance in high fructose feeding rats. Increase of insulin sensitivity by ginsenoside Rh2 was further identified using the plasma glucose lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated injection of ginsenoside Rh2 at the same dosing (1 mg/kg, 3 times daily) into STZ-diabetic rats for 10 days made an increase of the responses to exogenous insulin. Taken together, it can be concluded that ginsenoside Rh2 has an ability to improve insulin sensitivity and it seems suitable to use ginsenoside Rh2 as an adjuvant for diabetic patients and/or the subjects wishing to increase insulin sensitivity.