妊娠期高果糖膳食对子代胰岛素抵抗的影响

目的：探讨大鼠妊娠期高果糖膳食对子代胰岛素抵抗的影响。方法：正常饮食的成年雄性Wistar大鼠与雌性大鼠进行合笼,孕鼠随机分为5组,分别为正常对照组、正常剂量果糖组、高剂量果糖组、超高剂量果糖组和超高剂量蔗糖组,孕期每日分别给予2mL蒸馏水、2g/kg、6g/kg、18g/kg的果糖溶液以及18g/kg的蔗糖溶液灌胃,连续干预直至分娩,娩出仔鼠基础饲料喂养,并称量仔鼠体质量、检测空腹血糖。于第8周末检测空腹血糖、进行OGTT试验。于次日禁食12h后处死子代大鼠,麻醉、取血,测量血清胰岛素水平,计算胰岛素抵抗指数。结果：孕期连续干预后,娩出仔鼠出生体重：高剂量果糖组、超高剂量果糖组显著低于对照组（P＜0.05）;超高剂量果糖组娩出仔鼠空腹血糖显著高于对照组（P＜0.05）;OGTT试验：在30min处,高剂量果糖组、超高剂量果糖组以及超高剂量蔗糖组血糖值显著高于正常对照组及正常剂量果糖组（P＜0.05）,在120min处,高剂量果糖组、超高剂量果糖组及超高剂量蔗糖组血糖值显著高于正常对照组（P＜0.05）。高剂量果糖组、超高剂量果糖组及超高剂量蔗糖组的血清胰岛素含量和胰岛素抵抗指数都显著高于正常对照组和正常剂量果糖组（P＜0.05）。结论：妊娠期高果糖膳食会增加子代胰岛素抵抗及糖代谢的患病风险。     

槟榔碱对2型糖尿病大鼠肝脏胰岛素抵抗的作用

目的：探讨槟榔碱对2型糖尿病大鼠肝脏胰岛素抵抗的影响及其机制。方法：采用高果糖饲料饲养Wistar大鼠12周制备2型糖尿病大鼠模型,实验动物随机分为5组（n=8）：对照组、模型组、模型＋不同浓度的槟榔碱（0,0．5,1,5mg／kg）组。4周后通过检测血糖、血脂、胰岛素、RT-PCR检测肝脏组成型雄甾烷受体（CAR）、孕甾烷x受体（PXR）、糖代谢相关基因：葡萄糖-6-磷酸酶（G6Pase）、磷酸烯醇式丙酮酸羧激酶（PEPCK）和炎症相关因子：白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）mRNA表达,Western blot检测大鼠肝内p-AKT和葡萄糖转运体4（GLUT4）蛋白表达。结果：1,5mg／kg槟榔碱显著降低糖尿病大鼠体重、空腹血糖、空腹胰岛素、血脂和糖代谢相关基因及炎症相关因子mRNA水平,提高CAR、PXR mRNA水平及p-AKT、GLUT4蛋白水平。结论：槟榔碱可能通过提高CAR和PXR的表达,导致肝脏糖代谢关键酶PEPCK、G6Pase基因表达或者炎性因子肿瘤坏死因子-α（TNF-α）、白介素-6（n-6）表达降低,改善2型糖尿病大鼠肝脏胰岛素抵抗。     

黄连素调节肠道菌群治疗2型糖尿病的机制研究进展

2型糖尿病（type 2 diabetes mellitus,T2DM）主要由胰岛素分泌的相对和/或绝对缺乏引起,因其高发病率、高致残率已成为全球公共卫生领域面临的共同难题。由肥胖、氧化应激和慢性炎症等原因引起的胰岛素抵抗是其主要的发病机制之一。黄连素是一种安全性高、不良反应低、具有多种药理作用的天然的五环异喹啉类生物碱。然而黄连素在动物模型中的口服生物利用度极低,提示肠道菌群可能是其发挥多重药理作用的靶点。肠道菌群被称为“第二基因组”,通过调节代谢物、微生物－肠－脑轴、炎症反应、肠道激素和氧化应激影响T2DM。本文以综述的形式分析了黄连素调节肠道菌群在T2DM治疗中的作用机制,以期为T2DM及其他代谢性疾病的治疗提供新的思路。

     

胰岛素抵抗与糖尿病脑病

胰岛素抵抗(insulin resistance,IR)指胰岛素分泌量在正常水平时刺激靶细胞对葡萄糖的利用率减弱,或维持正常生理效应时需超常量的胰岛素,其主要机制是胰岛素信号通路敏感性下降。糖尿病脑病(diabetic encephalopathy,DE)是由糖尿病引起的认知功能障碍和大脑神经生理及结构的改变,目前认为胰岛素抵抗在糖尿病脑病的发生发展中起重要作用,本文从IR与DE的关系以及IR在DE中的主要作用机制作一综述.     

胰岛素抵抗在前列腺癌治疗前后动态变化的临床观察

目的:探讨胰岛素抵抗程度在前列腺癌治疗过程中动态变化及胰岛素抵抗程度与前列腺癌预后的关系。方法:选择前列腺癌惠者50名。平均年龄72岁。将前列腺癌患者根据治疗方法分为前列腺癌根治术组、手术去势组、药物去势组;根据有无复发转移分为复发转移组、无复发转移组。采用己糖激酶法测定空腹葡萄糖,放免法测定空腹胰岛素(Fasting serum insulin FINS)水平。运用HOMA模型中的胰岛素抵抗计算公式计算胰岛素抵抗指数(insulin resistance index IRI)。组间比较采用配对t检验。结果:前列腺癌患者在手术后的胰岛素抵抗指数明显下降,与手术前胰岛素抵抗指数存在统计学差异(P<0.05)。前列腺癌根治组的IRI值和手术去势组与药物去势组都存在统计学差异(P<0.05),但手术去势组和药物去势组两组之间不存在统计学差异(P>0.05)。前列腺癌治疗后无复发转移组的IRI值明显低于复发转移组,两组间IRI存在统计学差异(P<0.05)。结论:前列腺癌患者胰岛素抵抗程度与肿瘤治疗经过、效果有关。胰岛素抵抗指数有助于前列腺癌患者判断治疗效果,判断预后。     

强化饮食结合量化运动处方干预对IFG人群胰岛素抵抗的影响

目的探讨强化饮食结合运动处方干预对空腹血糖受损(IFG)人群胰岛素抵抗的影响。方法采取前瞻性观察研究方法,将2个社区150例IFG人群随机分成对照组和实验组进行为期3年的干预。其中实验组进行强化饮食结合量化运动处方干预,对照组不给予任何干预,观察两组患者各生化指标及胰岛素抵抗指数、胰岛素敏感指数。结果 (1)干预1年后,两组比较,FINS、IR差异无统计学意义(P0.05);TC、TG、HDL、LDL、血压、体重、腰臀比、ISI比较,差异有统计学意义(P0.05)。(2)干预3年后,两组各指标比较,差异均有统计学意义(P0.05),且较第1年有所改善。结论通过长期强化饮食结合量化运动处方干预,可降低IFG人群的胰岛素抵抗。     

明日叶查尔酮对2型糖尿病大鼠骨骼肌细胞胰岛素抵抗的干预作用

目的:研究明日叶查尔酮对2型糖尿病大鼠骨骼肌胰岛素抵抗的干预作用.方法:将2型糖尿病大鼠随机分成四组,高、中、低剂量组分别每日经口灌胃给予明日叶查尔酮30、10和5mg/(kg·bw),糖尿病对照组给予等量生理盐水.各组均以高脂饲料喂养.四周后采用葡萄糖氧化酶法检测空腹血糖;放射免疫法检测血清胰岛素含量;免疫组化法检测葡萄糖转运体1和葡萄糖转运体4蛋白表达水平.结果:经图像分析,高剂量组骨骼肌细胞中葡萄糖转运体1和葡萄糖转运体4蛋白表达平均光密度值分别为0.054± 0.0064和0.063±0.0139,均较糖尿病对照组显著性升高(P＜0.05).高剂量组空腹血糖和胰岛素水平分别为(12.3± 1.64)mmol/L和(25.65±3.34) (μIU/mL),均较糖尿病对照病显著性降低(P＜0.05).结论:明日叶查尔酮可增加2型糖尿病大鼠骨骼肌葡萄糖转运体l和葡萄糖转运体4蛋白表达水平,降低空腹血糖和胰岛素水平,改善胰岛素抵抗状况.     

格列美脲与沙格列汀联合治疗对2型糖尿病患者血糖控制、胰岛素抵抗及血脂的影响

目的:探讨2型糖尿病(T2DM)患者经格列美脲联合沙格列汀治疗后的临床效果,并分析其对患者血糖控制、胰岛素抵抗及血脂的影响。方法:选取我院2017年4月~2019年4月期间接收的88例T2DM患者,按乱数表法将患者分为研究组(n=44,格列美脲联合沙格列汀治疗)、对照组(n=44,沙格列汀治疗)。比较两组患者临床疗效、血糖、胰岛素抵抗及血脂指标,记录两组患者不良反应情况。结果:研究组治疗3个月后临床总有效率较对照组升高(P<0.05)。两组患者治疗3个月后空腹血糖(FBG)、餐后两小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)均下降,且研究组低于对照组(P<0.05)。两组患者治疗3个月后高密度脂蛋白(HDL-C)、空腹胰岛素(FINS)升高,且研究组高于对照组(P<0.05)。两组不良反应总发生率比较无差异(P>0.05)。结论:T2DM患者采用格列美脲联合沙格列汀治疗效果确切,可改善机体血脂水平及胰岛素抵抗,控制血糖水平,且用药安全性较好。     

阿司匹林增加胰岛素抵抗大鼠胰岛素敏感性的实验研究

目的　观察阿司匹林对高脂饮食大鼠胰岛素敏感性的影响。方法　灌服阿司匹林前后采用腹腔注射胰岛素耐量试验 (IITT)观察大鼠胰岛素的敏感性 ,并测定空服胰岛素、血糖和血脂等。结果　高脂饮食 4月、阿司匹林治疗 4周后 ,IITT发现高脂组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著高于正常对照组 (P <0 0 5或P <0 0 1 ) ;而阿司匹林治疗组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著低于高脂组 (P <0 0 5或P <0 0 1 ) ,与正常对照组差异无显著性。结论　大剂量阿司匹林有增加胰岛素敏感性和改善脂代谢紊乱的作用     

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats

Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, is reported to enhance glucose uptake in C2C12 myotubes in vitro, but the convincing evidence is lacking in vivo. In this study, PTF ameliorated insulin resistance and dyslipidemia, but failed to significantly increase body weight in type 2 diabetic rats induced by high-fat diet and low-dose streptozotocin.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg^–1 I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7–8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg^–1 urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 ± 16.9 mg dl^–1, n= 6, prior to insulin and 42.0 ± 8.4 mg dl^–1, n= 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg^–1, I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 ± 14.0 mg dl^–1, n= 10, prior to insulin and 386.6 ± 43.6 mg dl^–1, n= 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation. (Mol Cell Biochem 261: 105–110, 2004)     

Safety and efficacy of adeno-associated viral vector-mediated insulin gene transfer via portal vein to the livers of streptozotocin-induced diabetic Sprague-Dawley rats

BACKGROUND: Previous studies demonstrating the efficacy of insulin gene therapy have mostly involved use of adenoviral vectors or naked DNA to deliver the insulin gene. However, this procedure may not guarantee long-term insulin production. To improve the performance, we prepared recombinant adeno-associated viral vectors (rAAV) harboring the gene encoding a furin-modified human insulin under the cytomegalovirus (CMV) promoter [rAAV-hPPI(F12)]. METHODS: Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were used as a diabetic animal model. The levels of blood glucose, insulin, and HbA1c were measured to test the effect. An intraperitoneal glucose tolerance test was performed to test the capability of blood glucose disposal. Immunohistochemical staining and Northern blot analyses were performed to survey the expression pattern of the therapeutic insulin gene. RESULTS: STZ-induced diabetic Sprague-Dawley rats infused via the portal vein with rAAV-hPPI(F12) produced human insulin and after a 6-h fast were normoglycemic for over 90 days post-treatment, whereas diabetic rats treated with recombinant adenoviral vector harboring the hPPI(F12) gene [rAV-hPPI(F12)] were normoglycemic only for days 3 to 13 post-treatment. Insulin mRNA was detected mainly in the liver of the rAAV-hPPI(F12)-treated diabetic rats. The glucose tolerance capability of the rAAV-hPPI(F12)-treated diabetic rats was comparable to that of non-diabetic rats, even without injection of recombinant insulin. Furthermore, blood HbA1c concentrations in rAAV-hPPI(F12)-treated diabetic rats were reduced to almost the normal level. Importantly, studies of rAV or rAAV vector-dependent side effects on the targeted liver strongly suggested that only rAAV treatment caused no side effects. CONCLUSIONS: These results demonstrate that our rAAV-mediated in vivo insulin gene therapy provides safer maintenance of the insulin gene expression required for long-term and thus more effective blood glycemic control.     

南瓜多糖对糖尿病大鼠血糖和血脂的影响

目的：研究南瓜多糖对糖尿病大鼠血糖和血脂的影响。方法：Wistar大鼠腹腔注射四氧嘧啶后。将成模的糖尿病大鼠根据血糖和体重随机分为糖尿病组、消渴丸组和南瓜多糖组,同时设立正常对照组,并分别给予蒸馏水、消渴丸和南瓜多糖灌胃,每周测量体重一次,四周后测定空腹血糖、血清总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白和游离脂肪酸的含量。结果：糖尿病组大鼠体重下降,血糖显著升高,甘油三酯、总胆固醇、低密度脂蛋白和游离脂肪酸含量显著增加,而高密度脂蛋白含量显著降低;补充南瓜多糖和消渴丸后,体重逐渐增加,血糖显著下降,总胆固醇、甘油三酯、低密度脂蛋白和游离脂肪酸含量显著降低,高密度脂蛋白含量显著升高,并且南瓜多糖的降糖降脂效果优于消渴丸。结论：南瓜多糖能增加体重,降低糖尿病大鼠血糖、血脂,对糖尿病及其并发症有一定的作用。     

Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin levels in rats when administered before and after STZ-induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control.The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.     

Chromium picolinate supplementation improves insulin sensitivity in Goto-Kakizaki diabetic rats

Chromium picolinate (CrP) supplementation has been studied as a potential therapy of insulin resistance and lipid abnormalities. There have been some reports involving chromium supplementation in patients with diabetes, but the results are varied. The present study was conducted to assess the effects of CrP on insulin sensitivity and body weight in Goto-Kakizaki (GK) diabetic rats. We supplemented normal Sprague-Dawley (SD) rats and GK diabetic rats with supplemental CrP, 100 mg/kg/day once a day for 4 weeks. In the normal SD rats, the mean body weight of the control group increased by 50.5%, whereas that of the CrP-treated group increased by 65.9% (P < 0.05 vs control). Similarly, in the diabetic GK rats, CrP supplementation showed increased weight gain compared to the control group (133.4% vs 119.6% of the baseline weight, P < 0.01). Glucose tolerance tests (GTT) [ip injection of glucose; 2 g/kg] and insulin sensitivity tests [SQ injection of insulin (5 U/kg) plus ip injection of glucose (30 min after insulin injection)] were conducted. During insulin sensitivity tests at the end of treatment, the glucose levels were significantly lower in CrP-treated rats compared with the control rats (AUC_0→120; 113.1 ± 32.0 vs 170.5 ± 49.0 mg-min/mL, P < 0.05). During GTTs, the glucose levels and insulin concentrations in the CrP-treated rats were not different from those in the control rats.

The results of these studies suggest that CrP supplementation in GK diabetic rats leads to increase of weight gain and improvement of insulin sensitivity. This raises the possibility that CrP supplementation can be considered to improve carbohydrate metabolism in patients with type 2 diabetes mellitus.     

4种抗真菌药物对糖尿病大鼠血糖的影响

目的观察酮康唑、氟康唑、伊曲康唑和特比萘芬与胰岛素组合使用以及单独使用时对糖尿病大鼠血糖水平的影响。方法建立糖尿病大鼠模型,随机分为10组,每组5只。前4组皮下注射胰岛素的同时分别喂食4种抗真菌药物;第5组单独皮下注射胰岛素;第6—9组分别喂食4种抗真菌药物;第10组既不注射胰岛素也不喂食抗真菌药物。定时对糖尿病大鼠尾静脉采血,使用CX5PRO生化检测仪对其血糖进行检测。结果酮康唑、氟康唑和伊曲康唑分别与胰岛素合用时,可使糖尿病大鼠血糖降低（P〈0．05）;不与胰岛素合用时,氟康唑和伊曲康唑均可使糖尿病大鼠血糖升高（P〈0．05）;特比萘芬无论是否与胰岛素合用,对糖尿病大鼠的血糖水平均无影响（P〉0．05）。结论唑类抗真菌药物无论是否与胰岛素合用均会影响糖尿病大鼠的血糖水平,特比萘芬无论是否与胰岛素合用,都不会影响糖尿病大鼠的血糖水平。     

In vitro and in vivo prevention of HIV protease inhibitor-induced insulin resistance by a novel small molecule insulin receptor activator

Protease inhibitor (PI) therapy for the treatment of patients infected with human immunodeficiency virus is frequently associated with insulin resistance and diabetic complications. These adverse effects of PI treatment result to a large extent from their inhibition of insulin-stimulated glucose transport. Insulin receptor (IR) activators that enhance the insulin signaling pathway could be effective in treating this resistance. However, there are no agents reported that reverse inhibition of insulin action by PIs. Herein, we describe the effects of TLK19781. This compound is a non-peptide, small molecule, activator of the IR. We now report in cultured cells, made insulin resistant HIV by PI treatment, that TLK19781 both increased the content of insulin-stimulated GLUT4 at the plasma membrane, and enhanced insulin-stimulated glucose transport. In addition, oral administration of TLK19781 with the PI, indinavir improved glucose tolerance in rats made insulin resistant. These results suggest, therefore, that IR activators such as TLK19781 may be useful in treating the insulin resistance associated with PIs.     

Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats

We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model.