Effect of Genistein,a Soy Isof lavone,on Whole Body Insulin Sensitivity and Renal Damage Induced by a High-Fructose Diet

The study evaluates the effect of genistein, a soy isoflavone, on insulin sensitivity and renal functional and structural injury in rats rendered insulin-resistant by feeding on a high-fructose diet for 60 days. Fructose-fed animals (60 g /100 g) displayed insulin resistance as indicated by the measures of insulin sensitivity [insulin sensitivity index (ISI_0,120), quantitative insulin check index (QUICKI), and homeostatic model assessment (HOMA)]. Alterations in body weight, kidney weight, urine volume, plasma, and urine electrolytes accompanied by significant increases in plasma and urinary levels of urea, uric acid, creatinine, total protein, and albumin were observed in fructose-fed rats. Oxidative stress in kidney was noted by an elevation in lipid peroxides and a decline in glutathione (GSH). Insulin sensitivity and renal function were improved in fructose-fed rats administered genistein. Histological changes such as fatty infiltration and thickening of glomeruli observed in fructose-fed rats were also ameliorated when genistein was co-administered. The study shows that genistein improves insulin sensitivity and kidney function in a dietary model of insulin resistance. We suggest that genistein may have benefits for patients suffering from kidney disease associated with insulin resistance.     

胰岛素样生长因子-1对大鼠弥漫性脑损伤的保护

目的观察胰岛素样生长因子-1(insulin-likegrowthfactor-1,IGF-1)对大鼠弥漫性脑损伤(diffusebraininjury,DBI)皮层神经元死亡的影响,探讨应用IGF-1治疗脑损伤的可行性。方法用Marmarou方法制成大鼠DBI模型并分2d和5d组,伤后10min经侧脑室注入单剂2μgIGF-1,分别于2d和5d后观察室上区皮层神经元损伤变化。结果与对照组2d时(35±9)%和5d时(51±13)%相比,IGF-1治疗组的皮层神经元缺失显著减少犤2d组(24±6)%,F=5.19,P<0.05,5d组(30±7)%,F=13.47,P<0.01)。结论DBI后经侧脑室注入IGF-1可明显减少皮层神经元缺失,提示对DBI有治疗作用。     

The cytoplasmic Ca2+ response to glucose as an indicator of impairment of the pancreatic β-cell function

Abstract. The effects of glucose on the cytoplasmic Ca²⁺ concentration (Ca²⁺_i) regulating insulin release were investigated using pancreatic β-cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca²⁺_i followed by a rise, often manifested as high amplitude oscillations. The Ca²⁺_i-lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the β-cells were already depolarized by tolbutamide. Glucose-induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin- and noninsu-lin-dependent diabetes mellitus. Brief exposure of β-cells to 2–2 mmol 1^-1 streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca²⁺_i. The results indicate that glucose-induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defects in diabetes mellitus.     

Insulin stimulates the uptake of chylomicron remnants in cultured rat hepatocytes

The effects of insulin (10-1000 microU ml-1) on chylomicron remnant uptake and degradation were studied in hepatocyte monolayer cultures. Both uptake and degradation were stimulated by insulin. The degree of stimulation was influenced by cell density, being most pronounced in sparse cultures. The uptake was stimulated in a dose-dependent fashion and was noticed already at a physiological insulin level (100 microU ml-1). At this insulin concentration uptake was stimulated by approximately 50% (range 26-84%). As suggested by the increase in Vmax for the remnant uptake, the number of lipoprotein receptors on the hepatocytes was increased by 100 microU ml-1 of insulin. Apolipoprotein-E-free low density lipoproteins (LDL) competed much less efficiently for the uptake of radioactive remnants than did unlabelled remnant particles. About half of the stimulatory effect of insulin on the remnant uptake could, however, be abolished by adding an excess of LDL, indicating that at least part of the stimulation by insulin was due to increased activity of the LDL receptor. This study thus shows that physiological insulin levels increase chylomicron remnant uptake in hepatocyte monolayer cultures. It is assumed that the effect of insulin is to increase the number of lipoprotein receptors at the cell surface, and at least part of the stimulation is due to an increase in LDL receptor activity.     

Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension

Abstract. The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by the presence of insulin resistance, share some common genetic markers. A potential candidate is the Na⁺/H⁺ anti-porter, the increased activity of which is considered a marker of essential hypertension. This ion exchanger seems to be related to the Na⁺/Li⁺ countertransport, that is considered a marker of insulin resistance in essential hypertension and in type 1 diabetes mellitus. In this study we wished to clarify whether the activity of the Na⁺/H⁺ antiporter is increased not only in hypertensive subjects, but also in obese and type 2 diabetic patients, both in the presence and in the absence of arterial hypertension. The activity of the ion exchanger was measured in peripheral blood lymphocytes (PBL) by clamping intracellular pH (pH_i) at 5·8–6·2 and then detecting the rate of the proton efflux after sodium addition. In the absence of arterial hypertension, no significant difference in this parameter was observed in obese and type 2 diabetic patients in comparison with normal subjects. In the presence of arterial hypertension, there was a significant increase in the Na⁺-induced H⁺ efflux at the internal pH (pHi) values of 5·8 and 6·2 both in hypertensive controls and in hypertensive obese and type 2 diabetic patients (P= 0·05–0·0001 vs. normotensive subjects and patients). In particular, H⁺ efflux at pH 5·8 (mmol l^-1 min^-1) was 35·36 ± 2·48 in normotensive and 42·77 ± 1·63 in hypertensive control subjects (P= 0·045), 33·06 ± 1·88 in normotensive and 50·40 ± 5·21 in hypertensive obese patients (P= 0·009), 31·16 ± 1·84 in normotensive and 55·54 ± 5·83 in hypertensive type 2 diabetic patients (P= 0·0001). H⁺ efflux showed a significant correlation with both systolic (at pHi 5·8, r = 0·473, P= 0·001; at pHi 6·2, r = 0·357, P= 0·016) and diastolic blood pressure (at pHi 5·8, r = 0·600, P= 0·0001; at pHi 6·2, r = 0·555, P= 0·0001). Therefore, our study demonstrates that the hyperactivity of the Na⁺/H⁺ exchanger in peripheral blood lymphocytes is also a marker of arterial hypertension in obesity and in type 2 diabetes mellitus, and that the exchanger activity is not increased in these two conditions in the absence of arterial hypertension.     

IAA、ICA和GADA的年龄分布及与临床指标的关系研究

目的分析抗胰岛素抗体(IAA)、抗胰岛细胞抗体(ICA)和抗谷氨酸脱羧酶抗体(GADA)在患者中的分布情况及实验室指标的变化,探讨三种糖尿病相关抗体对疾病发生、发展变化的预示价值,为疾病治疗提供依据。方法分析2008-2018年在四川大学华西医院联合检测了IAA、ICA和GADA三种抗体患者的相关信息。将抗体阳性患者分为3个不同的年龄组(<40岁、40~59岁、>59岁),比较抗体检测结果组合在各年龄组间分布差异,分析抗体阳性患者疾病分布情况。以抗体阳性分组,分析三种抗体单项阳性组(单阳组)患者实验室指标检测结果的差异。结果三种抗体在不同年龄组间的分布差异无统计学意义(P>0.05);糖尿病患者人群IAA抗体单项阳性占65.08%;三种抗体主要存在于糖尿病患者中(占92.03%),其他疾病(如癌症、低血糖、系统性红斑狼疮)患者也可出现。碱性磷酸酶在IAA单阳组中的水平显著低于ICA单阳组(P<0.05);尿酸和肌酐在IAA单阳组中的水平显著高于GADA单阳组(P<0.05);球蛋白和肾小球滤过率在IAA单阳组水平显著低于GADA单阳组(P<0.05);空腹胰岛素在IAA单阳组水平显著高于ICA和GADA单阳组(P<0.05)。结论IAA、ICA和GADA三种抗体在各年龄组分布相近。IAA可作为糖尿病抗体检测的首选指标,IAA阳性糖尿病患者更应该注意其并发肾功能损害的风险。     

运动对糖尿病大鼠脑细胞膜胰岛素受体的影响

目的观察链脲佐菌素（ＳＴＺ）糖尿病大鼠脑细胞膜胰岛素受体的特性及运动训练对其的影响。方法３０只ＳＤ大鼠分为三组：糖尿病非运动组；糖尿病运动组；正常对照组。糖尿病运动组大鼠进行６周游泳训练。结果糖尿病运动组大鼠与糖尿病非运动组大鼠相比，血糖浓度明显降低，而二组糖尿病大鼠血胰岛素浓度均低于正常组。三组大鼠比较，脑细胞膜的胰岛素受体最大专一性结合、受体亲和力常数及受体浓度均无显著性差异。结论运动训练能降低糖尿病大鼠的血糖水平，但血糖、血胰岛素及运动对脑细胞膜的胰岛素受体无明显影响     

血清瘦素及游离脂肪酸在肥胖患者中的致胰岛素抵抗作用

目的研究瘦素及游离脂肪酸(FFA)对肥胖患者胰岛素抵抗(IR)状态形成的作用.方法按体重指数(BMI)将实验对象(82例)分为肥胖组及对照组;测量身高、体重、腰围、臀围,计算体重指数、脂肪百分比(?t)、腰臀比(WHR)及胰岛素敏感指数(ISI);葡萄糖氧化酶法测定血清葡萄糖;化学发光免疫分析法测定血清胰岛素;生化比色法测定血清游离脂肪酸.结果肥胖人群中血清瘦素、FFA水平明显高于对照组(P＜0.01),且升高幅度与反应肥胖度的各项指标(BMI、WHR、?t)呈显著正相关,与ISI呈负相关.结论瘦素及FFA是重要的致IR物质,也是IR存在时重要标志.