灵菊七提取物降血糖作用的实验研究

考察不同剂量的灵菊七提取物对糖尿病小鼠血糖、口服糖耐量、血清胰岛素水平的影响。采用雄性昆明小鼠腹腔注射四氧嘧啶制备糖尿病小鼠模型,分别以灵菊七提取物低、中、高剂量进行灌胃,连续21天,灌胃结束后观察血糖、口服糖耐量、血清胰岛素水平的变化。结果显示灵菊七提取物各剂量组均能降低糖尿病小鼠的血糖,改善口服糖耐量和提高血清胰岛素水平,并具有一定的量效、时效关系。     

评估胰岛素分泌及胰岛素敏感性选择降糖药物的临床多中心研究

目的本研究主要就胰岛素敏感性以及胰岛素分泌情况展开分析讨论,以此来为2型糖尿病患者在治疗过程中降糖药物的选择提供参考依据。方法选择我院2008年10月至2012年10月所收治的322例被诊断为2型糖尿病患者作为研究对象,根据患者的胰岛素分泌情况将其分为正常组与低下组,将正常组患者分为A、B组,低下组患者分为C、D组;A组患者给予罗格列酮以及瑞格列奈进行治疗;B组患者给予二甲双胍进行治疗;C组患者给予罗格列酮以及瑞格列奈进行治疗;D组患者给予格列吡嗪进行治疗,比较四组患者的治疗效果。结果四组患者在用药3、6个月后的HbA1c、餐后2 h血糖、空腹血糖与基线值存在明显差异,具有统计学意义,P<0.05。结论在对2型糖尿病患者进行临床治疗时,通过对患者的病理以及生理情况进行全面评估,并采用正确的方法来对患者进行药物治疗,可以对患者的糖代谢紊乱情况进行纠正。瑞格列奈及格列吡嗪可以在一定程度上增加糖尿病患者的真胰岛素以及一相胰岛素的分泌水平。     

黄芪多糖对MIN6细胞增殖、凋亡及胰岛素分泌的影响

目的:研究不同浓度黄芪多糖(Astragalus polysaccharide,APS)对胰岛MIN6细胞的增殖活性、细胞凋亡及胰岛分泌功能的影响。方法:用不同浓度APS(0,10,100和1 000μg.mL-1)干预MIN6细胞48 h,采用MTT法测细胞增殖活性,流式细胞仪检测细胞凋亡,分别用3和30 mmol.L-1葡萄糖刺激各组MIN6细胞,胰岛素放免试剂盒检测胰岛素分泌功能。结果:与对照组(0μg.mL-1)比较,100μg.mL-1 APS组MIN6细胞增殖活性升高(P<0.05);10和100μg.mL-1 APS组MIN6细胞凋亡率有下降趋势,而1 000μg.mL-1 APS组MIN6细胞凋亡率明显增加(P<0.05);10和100μg.mL-1 APS组MIN6细胞胰岛素分泌功能显著增强(P<0.05),而1 000μg.mL-1 APS组MIN6细胞胰岛素分泌功能有下降趋势。结论:10和100μg.mL-1 APS使MIN6细胞增殖活性升高、细胞凋亡率下降以及胰岛素分泌功能升高;1 000μg.mL-1 APS使MIN6细胞增殖活性下降、细胞凋亡率升高及胰岛素分泌功能下降。     

一氧化氮对大鼠胰岛细胞胰岛素分泌的影响

目的：研究一氧化氮(NO)对胰岛细胞分泌胰岛素的影响及其机制。方法：①采用经胰管注射胶原酶技术分离大鼠胰岛，葡聚糖(Ficoll)不连续密度梯度方法离心纯化胰岛；②用硝普钠(SNP)作为NO供体，硫酸亚铁(FeS04)作为NO抑制剂，放射免疫法检测胰岛细胞胰岛素分泌量。结果：NO明显抑制胰岛细胞胰岛素基础分泌和葡萄糖刺激的胰岛素释放，FeSO4能阻断这种作用(P值均＜0．05)。结论：NO能明显抑制大鼠胰岛细胞的分泌功能，这可能是体内胰岛细胞损害的因子之一。     

促肝细胞生长素对糖尿病大鼠降糖作用的研究

目的 研究促肝细胞生长素的降糖作用机制。方法胰岛素注射液(2u／kg，im)为阳性对照，0．9％NaCl(1mL，iv)为阴性对照，分别给正常大鼠和链脲佐菌素性糖尿病大鼠促肝细胞生长素(20mg/kg，iv)，研究促肝细胞生长素的降糖作用；给链尿佐菌素性糖尿病大鼠胰岛素注射液(2U／k，im)合并促肝细胞生长紊(20mg/kg，iv)，研究药物相互作用机制；给糖尿病大鼠分别以5组剂量(2．5，5．0，10．0，20．0，40．0mg/kg，iv)促肝细胞生长素，研究该药物降糖作用的量效关系。利用高效液相色谱法对组分进行分析，研究促肝细胞生长素中是否含有胰岛素。结果促肝细胞生长素(20mg/kg，iv)对正常大鼠无降糖作用，对糖尿病大鼠具有降糖作用。与胰岛素合并用药，能延长胰岛素降糖作用时间，增强促肝细胞生长素降糖作用，但未见低血糖出现。量效关系研究表明，给药剂量大于20mg/kg时，加大剂量不能提高药品的降糖作用，不导致低血糖。促肝细胞生长素不含有与胰岛素保留时间相同的组分。结论促肝细胞生长素含有降糖成分，与胰岛素合并使用，效果优于单独使用。     

新磺酰脲类促胰岛素分泌药-格列美脲的作用优势

目的:解析磺酰尿类促胰岛素分泌药格列美脲的作用优势,以期为临床合理应用提供参考。方法:采用国外文献进行综述评价。结果与结论:格列美脲作为一种长效降糖药,作用具有双重作用机制。降糖活性更突出。主要不良反应有食欲不佳、恶心、呕吐等。     

甘精胰岛素联合促胰岛素分泌剂治疗2型糖尿病的疗效观察

目的探究甘精胰岛素联合促胰岛素分泌剂治疗2型糖尿病疗效。方法将收治于我院86例2型糖尿病患者作为研究对象,入选时间为2016年2月至2017年2月,按随机数字表法分为2组,各43例;对照组患者给予常规治疗,观察组患者给予甘精胰岛素及促胰岛素分泌剂联合治疗,对比两组患者的血糖指标、低血糖发生率及胰岛素每日平均用量。结果从血糖指标来看,对照组与观察组治疗前后餐后2 h血糖及空腹血糖指标变化幅度相比差异明显,两组数据比较具有统计学意义(P <0.05);从低血糖发生率及胰岛素每日平均用量指标来看,对照组与观察组各项指标变化幅度相比差异显著,两组数据比较具有统计学意义(P <0.05)。结论 2型糖尿病患者实行甘精胰岛素及促胰岛素分泌剂联合治疗效果显著,能有效控制血糖指标预防发生低血糖现象。因此值得在临床治疗中使用及推广。     

黄柏中几种生物碱的分离、鉴定及促胰岛素分泌活性筛选

研究黄柏(Phellodendron chinense)的生物碱成分极其促胰岛素分泌。采用硅胶等色谱方法进行分离、纯化,通过理化性质及波谱方法鉴定其化学结构。从黄柏的生物碱部分分离得到3个化合物,分别为小檗碱(1)、药根碱(2)、黄柏碱(3)。研究发现,化合物小檗碱(1)具有促胰岛素分泌活性。     

促胰岛素分泌肽的聚乙二醇化修饰和体内外生物活性研究

通过基于Byetta结构的促胰岛素分泌肽类似物的PEG修饰和筛选,以期获得一种长效促胰岛素分泌肽修饰物。利用化学合成的方法获得C末端突变成半胱氨酸的Byetta类似物(Ex4C),再用不同分子质量大小的马来酰亚胺活化的mPEG(MAL-mPEG)对其半胱氨酸的游离巯基进行定点修饰,修饰后产物用阴离子交换色谱和反相色谱进行纯化。通过测定其体外刺激RINm5F细胞释放cAMP的水平,以及体内对STZ模型小鼠的降血糖作用来评价其生物活性。MAL-mPEG化的促胰岛素分泌肽的SDS-PAGE及RP-HPLC纯度均达98%以上,且修饰位点专一;促胰岛素分泌肽经5 k、20 k、35 k分子质量大小的mPEG修饰后体外刺激RINm5F细胞释放cAMP的ED50分别为1.61 ng/mL、15.68 ng/mL、32.95 ng/mL;3种修饰物在相同剂量(40μg/kg)皮下给药对正常小鼠和STZ模型小鼠体内均有明显的降血糖作用,维持降血糖时间分别达24 h、48 h和72 h。     

胰岛素滴鼻剂的降糖作用

笔者在国内首次研制了胰岛素的新剂型——胰岛素滴鼻剂。通过对实验动物的降糖实验,发现滴鼻剂效价P_T=259.4u/ml,其降糖能力相当于胰岛素注射剂的51.88％。     

Investigation of morin‐induced insulin secretion in cultured pancreatic cells

Morin is a flavonoid contained in guava that is known to reduce hyperglycemia in diabetes. Insulin secretion has been demonstrated to increase following the administration of morin. The present study is designed to investigate the potential mechanism(s) of morin‐induced insulin secretion in the MIN6 cell line. First, we identified that morin induced a dose‐dependent increase in insulin secretion and intracellular calcium content in MIN6 cells. Morin potentiated glucose‐stimulated insulin secretion (GSIS). Additionally, we used siRNA for the ablation of imidazoline receptor protein (NISCH) expression in MIN6 cells. Interestingly, the effects of increased insulin secretion by morin and canavanine were markedly reduced in Si‐NISCH cells. Moreover, we used KU14R to block imidazoline I₃ receptor (I‐3R) that is known to enhance insulin release from the pancreatic β‐cells. Without influence on the basal insulin secretion, KU14R dose‐dependently inhibited the increased insulin secretion induced by morin or efaroxan in MIN6 cells. Additionally, effects of increased insulin secretion by morin or efaroxan were reduced by diazoxide at the dose sufficient to open K_ATP channels and attenuated by nifedipine at the dose used to inhibit L‐type calcium channels. Otherwise, phospholipase C (PLC) is introduced to couple with imidazoline receptor (I‐R). The PLC inhibitor dose‐dependently inhibited the effects of morin in MIN6 cells. Similar blockade was also observed in protein kinase C (PKC) inhibitor‐treated cells. Taken together, we found that morin increases insulin secretion via the activation of I‐R in pancreatic cells. Therefore, morin would be useful to develop in the research and treatment of diabetic disorders.     

Effects of oral monosodium (L)-glutamate on insulin secretion and glucose tolerance in healthy volunteers

AIMS: To investigate the effects of glutamate on insulin secretion and glucose tolerance in humans. METHODS: Monosodium (L)-glutamate (10 g) was given orally in a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged 19-28 years, with an oral (75 g) glucose load. RESULTS: The 75 min insulin response (AUC(0,75 min)), up to tmax of glutamate kinetics, was significantly correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049). Glucose tolerance was not affected. CONCLUSIONS: Oral (L)-glutamate enhances glucose-induced insulin secretion in healthy volunteers in a concentration-dependent manner.     

Effect of sparteine sulphate upon basal and nutrient-induced insulin and glucagon secretion in normal man

Summary Infusion of a therapeutic dose of sparteine sulphate, increased the basal plasma insulin level and lowered plasma glucose. When an intravenous glucose tolerance test was performed with the infusion, the total insulin AUC was significantly larger than in absence of sparteine (2025 vs 1464 µU/ml×min), plasma glucose levels were lower and improved glucose utilization was observed (k_g:1.55 vs 1.39%). In the presence of arginine, sparteine sulphate stimulated both and cells, increasing both the total insulin (1907 vs 1516 µU/ml×minp<0.02) and total glucagon AUCs (7616±654 vs 6789±707 pg/ml×minp<0.01). Thus, sparteine sulphate increased both basal and nutrient-induced insulin and glucagon secretion in normal man.This work was presented in part at the XII Congress of the International Diabetes Federation, Madrid, 23–28/9/1985     

Impairment of insulin secretion in man by nifedipine

Summary The effect of nifedipine, a calcium antagonist, on carbohydrate metabolism and insulin secretion was evaluated in patients who required treatment with this drug. 20 subjects underwent two oral glucose tolerance tests (100 g), one under basal conditions, and the other after ten days of treatment with nifedipine 30 mg/day by mouth, in three divided doses. 10 subjects had normal glucose tolerance; in them nifedipine administration reduced the insulin response to oral glucose in the first 60 min, but improved glucose tolerance. The other 10 subjects had impaired glucose tolerance and nifedipine treatment resulted in a further reduction both of insulin secretion and glucose tolerance. No such effects were seen in the placebo (weight- and disease-matched) group. The mechanism by which nifedipine influences carbohydrate metabolism and insulin secretion is discussed.     

Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients

Summary The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique.Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment.The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.     

高甘油三酯并糖调节异常及正常者的胰岛素抵抗及胰岛素分泌的研究

目的:了解高甘油三酯并糖调节异常(IGR)[包括空腹血糖受损(IFG)或/和糖耐量减低(IGT)者]及正常(NGT)者的胰岛素抵抗及胰岛素分泌。方法:在体检人群中筛选出高甘油三酯并IGR及NGT者62人及健康者14人为研究对象,测血压、身高、体重、腰围、臀围,计算体重指数(BMI)及腰臀比(腰/臀)。经口服葡萄糖耐量试验(OGTT)测血糖(PG),同时检测甘油三酯(TG)及真胰岛素(TINS)、胰岛素原(PINS),根据血糖和TG结果将研究对象分为四组。①组(健康对照组):为NGT和TG正常者14人,②组(NGT+HTG):为NGT而高TG者即20人,③组(IFG/IGT+HTG):IFG或IGT伴高TG者23人,④组(IFG+IGT+HTG):IFG并IGT伴高TG者19人,四组均排除高血压病、肥胖及其它疾病。根据稳态模型公式计算各组的胰岛素抵抗指数(HOMA-IR),HOMA胰岛β细胞功能指数(HOMA-β),胰岛素快速反应指数(AIR)。结果:四组的BMI、腰/臀,真胰岛素,胰岛素原水平呈现①②③④组依次递增的趋势,③④组的HOMA-IR有别于①②组,四组的HOMA-β依次递减,差异均有显著性,P<0.05~0.000。结论:高甘油三酯并IGR及NGT者已出现胰岛素抵抗、胰岛素分泌及胰岛β细胞功能变化。     

Decrease in insulin secretion related to hypocalcemia induced by a high dose of zinc in rats

A single oral administration of zinc (Zn), sufficient to induce hypocalcemia, caused a decrease in glucose tolerance in fasted rats. This decrease resulted from reduction of insulin secretion. The restoration of Zn-induced hypocalcemia completely prevented the decrease in glucose tolerance and insulin secretion. These results suggest that the effect of Zn administration on insulin secretion in rats is a consequence of hypocalcemia.     

Effects of a new diuretic piretanide on glucose tolerance,insulin secretion and 125I-insulin binding

Summary The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and ¹²⁵I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glyco-haemoglobin A₁ measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 µU/ml; p<0.05). Glucagon — stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 µU/ml, p<0.05) and after 8 weeks (1.67 vs. 2.90 µU/ml, p<0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of ¹²⁵I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.     

Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion

AIM: To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS: Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kgwere treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral glucose tolerance was determined, and for 8 weeks, the fasting blood glucose, insulin, lipid series were determined. In insulin secretion experiments, berberine 93.75, 187…