消渴汤方剂对Ⅱ型糖尿病大鼠GLP-1分泌的影响

目的　探讨消渴汤方剂对Ⅱ型糖尿病大鼠类胰高血糖素肽 1(GLP 1)水平和血糖分泌的影响, 为Ⅱ型糖尿病的治疗提供新的思路。方法　应用酶联免疫吸附(ELISA)方法测定正常组、Ⅱ型糖尿病模型组 和口服消渴汤大鼠组血浆GLP 1和血糖水平。结果　Ⅱ型糖尿病大鼠血糖水平明显高于正常大鼠,口服消渴 汤大鼠GLP 1水平明显高于Ⅱ型糖尿病大鼠、血糖水平低于Ⅱ型糖尿病大鼠,对正常组大鼠无影响。结论　 消渴汤使Ⅱ型糖尿病大鼠GLP 1水平升高、血糖水平降低。     

ASS对实验性Ⅱ型糖尿病大鼠胰岛素和C肽分泌作用研究

目的 研究刺五加叶皂甙（ASS）对实验性Ⅱ型糖尿病大鼠胰岛素和C肽分泌作用影响。方法 应用放射免疫学方法对正常组和Ⅱ型糖尿病模型组大鼠（尾静脉注射链尿佐菌素25mg/kg加高脂，高热、高能量喂养）。在给予ASS后其空腹及口服葡萄糖后血浆中胰岛素和C肽变化测定。结果 ASS可增强Ⅱ型糖尿病大鼠胰岛素和C肽分泌，对正常大鼠无影响。结论 ASS可以促进Ⅱ型糖尿病大鼠胰岛素和C肽分泌。     

刺五加叶皂甙对Ⅱ型糖尿病大鼠GLP-1和血糖分泌的影响

目的　研究刺五加叶皂甙 (acanthopanaxsenticosussaponin ,Ass)对实验性Ⅱ型糖尿病 (非胰岛素依赖型糖尿病 ,non insulindependentdiabetesmellitus,NIDDM)大鼠胰高血糖素样肽 1(glucagon likepeptide 1,Glp 1)和血糖的作用。方法　选用雄性Wistar大鼠 5 0只 ,用链尿佐菌素 2 5mg/kg加高脂、高糖、高热量饲养制成Ⅱ型糖尿病大鼠模型。应用放射免疫分析测定给予Ass后其空腹及口服葡萄糖后血浆中Glp 1和血糖变化。 结果　与正常组大鼠比较 ,Ass可使Ⅱ型糖尿病大鼠空腹及口服葡萄糖后Glp 1分泌升高、血糖水平降低。 结论　Ass对Ⅱ型糖尿病大鼠具有一定的治疗作用     

C肽对GK大鼠糖尿病肾病的影响

目的研究C肽对糖尿病肾病GK大鼠肾脏病理和肾脏功能的影响及相关机制。方法SPF级自发性糖尿病GK大鼠,在糖尿病发病并且24小时尿蛋白超过300mg后,随机分为3组：C肽治疗组、空白对照组和胰岛素治疗组,每组8只,持续治疗12周。以同龄的正常Wistar大鼠作为正常组。治疗前及治疗后每4周检测各组大鼠血糖、24小时尿蛋白以及24小时尿白蛋白。治疗结束后,取各组大鼠肾脏,透射电子显微镜观察大鼠肾脏肾小球病理改变。采用实时定量PCR、westernblot以及免疫组织化学的方法检测肾小球RAGE、PKC－6和PKA的表达。采用单因素方差分析评价各组间的差异。结果与正常组相比,空白对照组的血糖、24小时尿蛋白和24小时尿白蛋白都明显升高：虽然C肽治疗组大鼠的血糖没有明显改变,但24小时尿蛋白和24小时尿白蛋白与空白对照组相比都明显减少;胰岛素治疗组的血糖明显降低,但24小时尿蛋白和24小时尿白蛋白与空白对照组相比没有明显差异。病理学检查显示,与空白对照组相比,C肽治疗组大鼠的肾小球硬化、肾小球系膜增生、基底膜厚度和足细胞的形态都明显改善,而胰岛素治疗不具有类似的作用。实时定量PCR、westernblot和免疫组织化学结果显示,C肽能够显著下调RAGE和PKC—β在糖尿病肾病大鼠肾小球的表达,并显著上调PKA的表达;而胰岛素仅能明显下调RAGE,对PKC、PKA的表达没有明显调节作用。结论C肽可能通过下调。肾小球毛细血管RAGE、PKC－β的表达和上调PKA的表达而改善GK大鼠的糖尿病肾病。     

化学发光免疫分析测定胰岛素及C肽在2型糖尿病诊断中的临床应用

应用化学发光免疫分析测定50例2型糖尿病患者及30名正常人血清胰岛素和C肽含量并对测定结果进行分析,了解糖尿病患者糖代谢和胰岛β细胞的功能。结果显示,2型糖尿病患者空腹胰岛素和C肽高于正常人（P＆lt;0.05）,餐后1h对照组出现峰值,餐后2h糖尿病组达到高峰,餐后3h仍不能恢复至正常水平。结论：化学发光免疫分析检测胰岛素及C肽可用于临床,帮助糖尿病分型,判断病情严重程度及指导治疗。     

不同浓度红景天苷对Ⅱ型糖尿病大鼠骨骼肌磷脂酰肌醇-3-激酶及葡萄糖转运蛋白-4表达的影响

目的:观察不同浓度红景天苷对Ⅱ型糖尿病大鼠血糖、血脂及骨骼肌磷脂酰肌醇-3-激酶(PI3K)和葡萄糖转运蛋白-4(GLUT4)表达含量的影响,探讨红景天苷降糖改善胰岛素抵抗的可能机制。方法:采用小剂量链脲佐菌素加高脂高热量饲料喂养方法建立Ⅱ型糖尿病大鼠模型,将建模成功后大鼠随机分为糖尿病模型组(DM),二甲双胍治疗组,红景天苷高、中、低剂量组。按规定药物剂量灌胃12周后测血糖、血脂及胰岛素水平,处死大鼠,取后肢骨骼肌,免疫印迹检测组织中PI3K和GLUT4的表达水平。结果:与对照组比较,DM组大鼠骨骼肌细胞中PI3K和GLUT4表达明显降低;与DM组比较,红景天苷各治疗组骨骼肌细胞中PI3K和GLUT4的表达明显增强。结论:红景天苷可能通过增强大鼠骨骼肌组织细胞中PI3K和GLUT4的表达以改善Ⅱ型糖尿病胰岛素抵抗。     

肥胖和老年2型糖尿病患者血清C肽、胰岛素、血糖的关系

目的 通过口服葡萄糖耐量实验,观察血清C肽、胰岛素释放水平,计算胰岛素敏感指数,探讨肥胖对老年2型糖尿病患者几个指标的影响.方法 选择本院老年2型糖尿病患者136例,根据1999年WHO糖尿病的诊断标准及患者的体重指数分为非肥胖糖尿病组60例和肥胖糖尿病组76例;另选健康检查者92例,分为非肥胖对照组40例和肥胖对照组52例.采用己糖激酶法测定血糖,采用时间分辨荧光免疫法测定C肽和胰岛素.结果 非肥胖糖尿病组与非肥胖对照组,肥胖糖尿病组与肥胖对照组,肥胖对照组与非肥胖对照组,非肥胖糖尿病组与肥胖糖尿病组两两比较,各时间点C肽和胰岛素水平差异均有统计学意义（P ＜0.05或P＜0.01）.肥胖对照组与非肥胖对照组,非肥胖糖尿病组与肥胖糖尿病组两两比较,各时间点血糖水平差异均无统计学意义（P＞0.05）,肥胖者服糖后血糖下降更慢.结论 肥胖影响老年2型糖尿病患者的C肽和胰岛素,为该病的危险因子.     

短期胰岛素治疗新发Ⅱ型糖尿病的临床观察

目的观察短期胰岛素治疗对新发Ⅱ型糖尿病病人的胰岛β细胞功能和血糖控制的影响。方法采用自身前后对照，观察18例新诊断Ⅱ型糖尿病人接受短期胰岛素强化治疗前后血糖及C肽释放试验的变化，了解胰岛素治疗前后胰岛β细胞功能的变化。结果经短期胰岛素治疗后，患者血糖明显下降，各点C肽水平明显升高，且有高峰出现，胰岛β细胞功能有恢复。结论对明显高血糖的新发Ⅱ型糖尿病患者短期胰岛素治疗，能显著改善其胰岛β细胞功能，有利于以后长远控制好血糖。     

1型糖尿病及肥胖儿童血清瘦素水平及与其它常用指标相关性分析

目的比较1型糖尿病及肥胖儿童血清瘦素水平。方法以EL1SA方法测定35例1型糖尿病、32例肥胖及35例健康儿童的血清瘦素水平。35例1型糖尿病患者中 ,7例为新患糖尿病伴酮症酸中毒的患者。通过测定C -肽水平来评估胰岛素的分泌。C -肽、血糖、糖化血红蛋白按常规方法测定。结果糖尿病患者血清瘦素水平低于对照组 (P<0.001)。肥胖儿童血清瘦素及C -肽水平高于糖尿病组及对照组。在糖尿病新患者中 ,经1个月的胰岛素治疗后 ,血清瘦素水平未有任何变化 (P>0.05)。在联合组中 ,瘦素与体重指数 (bodymassindex,BMI)及C -肽呈正相关(P<0.001) ,而与血糖及糖化血红蛋白呈负相关(P<0.05)。结论1型糖尿病患儿血清瘦素水平低可能与代谢控制有关的慢性胰岛素缺乏引起的。瘦素及胰岛素在保持身体体重稳定的过程中可能起着补充作用。     

Cell apoptosis in sinuatrial node in type Ⅱ diabetes rat

目的:探讨Ⅱ型糖尿病大鼠窦房结(SAN)细胞的凋亡及胰岛素对其的影响.方法:高糖高脂饮食加小剂量链脲佐菌素腹腔注射制备Ⅱ型糖尿病大鼠模型,随机分为正常对照组、糖尿病组和胰岛素治疗组,窦房结组织行TUNEL染色法,检测窦房结细胞凋亡指数的变化.结果:对照组窦房结内可见散在的凋亡细胞,多分布于窦房结中央；在糖尿病组,可见窦房结内凋亡细胞明显增加,呈不均一分布,凋亡细胞数量多,集中在窦房结中央；虽然治疗组凋亡细胞数量比糖尿病组减少,但仍比对照组多见.结论:Ⅱ型糖尿病大鼠窦房结16周后出现结内细胞凋亡明显增加；Ⅱ型糖尿病大鼠行胰岛素降低血糖后可减少结内凋亡细胞发生.     

肥胖型NIDDM患者胰岛素受体测定的临床意义

本文采用放射免疫法及放射受体法分别测定了１４名健康人及２６名肥胖型ＮＩＤＤＭ患者血浆胰岛素、Ｃ－肽及全血细胞胰岛素受体（ＩＮＳＲ）。结果显示ＮＩＤＤＭ患者血浆胰岛素及Ｃ－肽水平均显著高于健康人（Ｐ〈０．０５），而胰岛素受体数目显著减少（Ｐ〈０．０１）。提示肥胖型ＮＩＤ－ＤＭ存在胰岛素受体缺陷，且以数量少而高亲和力的功能性受体为主要标志。     

C肽、胰岛素在实验性NIDDM大鼠GT实验中的变化

为探讨C肽 (C -P)、胰岛素 (INS)在非胰岛素依赖型糖尿病 (NIDDM )模型糖耐量 (GT)实验中的变化 ,用小剂量尾静脉注射链脲佐菌素 (STZ)加喂高热量饮食形成NIDDM鼠模型 ,对GT实验中C -P、INS的变化进行观察。结果显示 :与对照组比 ,实验组INS升高的高峰时间是在两小时 ,C -P同INS反映一致 ,高峰推迟 (P <0 .0 5 )。提示 :血中C -P测定能准确反映胰腺内生INS水平 ,小剂量注射STZ加喂高热量饮食这种方法形成的NIDDM鼠模型非常理想     

当归内酯联合消渴丸对糖尿病肾病大鼠肾脏保护及血管内皮生长因子信号通路的调节作用

目的 探讨当归内酯联合消渴丸对糖尿病肾病大鼠血糖调节、肾脏保护及其体内血管内皮生长因子(VEGF)信号通路的调节作用.方法 75只大鼠随机分为5组,分别为对照组、模型组、消渴丸组、当归内酯组、当归内酯联合消渴丸组,每组15只.除对照组外,其余大鼠建立糖尿病肾病大鼠模型,消渴丸组、当归内酯组、当归内酯联合消渴丸组分别灌胃...     

Transient effect of the combination of insulin and sulfonylurea (glibenclamide) on glycemic control in non-insulin dependent diabetics poorly controlled with insulin alone

In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p less than 0.001), 24-hour urinary glucose (p less than 0.01) and glycohemoglobin (HbA1) concentrations (p less than 0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p less than 0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA1 concentrations (r = 0.56, p less than 0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.     

Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM rats.

The inhibition of ATP-sensitive K+(KATP) channels in pancreatic beta cells is a key step of insulin secretion induced by glucose. Glucose-induced insulin secretion from the beta cells is selectively impaired in patients with noninsulin-dependent diabetes mellitus (NIDDM) and in animal models of it. In order to clarify the site of this abnormal glucose response, we studied the effects of insulin secretagogues and sulfhydryl oxidizing agent, 2,2''-dithio-bis (5-nitropyridine) (DTBNP), on KATP channels in single beta cells of neonatally streptozotocin-induced NIDDM rats. We used the patch-clamp technique in cell-attached mode (Vpipette = 0 mV). The inhibitory response to glucose of KATP channels was lacking in NIDDM rats, indicating reduced sensitivity to glucose of the channels. Glyceraldehyde (2-5 mM) in the diabetic beta cells elicited the same KATP channel inhibition as that obtained in controls. In contrast, dihydroxyacetone (DHA, 2-10 mM) sensitivity of KATP channels was significantly reduced in the beta cells of NIDDM rats. KATP channels in the diabetic beta cells were rapidly inhibited by 50 microM DTBNP, just as in the normal beta cells, suggesting that KATP channel function was normal. This indicates that one of the sites responsible for impaired glucose-induced insulin secretion in the pancreatic beta cells of NIDDM rats is located in the glycerol phosphate shuttle.     

Role of sympathetic tone in the loss of syringin-induced plasma glucose lowering action in conscious Wistar rats

Syringin is an active principle purified from the rhizome and root parts of Eleutherococcus senticosus (Araliaceae). The present study is designed to clarify the role of sympathetic activation in the insulinotropic effect of syringin. Plasma glucose lowering effect accompanying with the increase of plasma insulin and C-peptide were obtained in pentobarbital anesthetized Wistar rats 60min after an intravenous (i.v.) injection of syringin (100 microg/kg). However, neither the plasma glucose lowering action, nor the raised plasma levels of insulin and C-peptide can be obtained in conscious rats received same syringin treatment. Otherwise, the insulin-releasing and plasma glucose lowering actions of syringin (100 microg/kg, i.v.) were appeared in conscious rats under chemical sympathectomy using an intraperitoneal injection of guanethidine. In addition, plasma glucose lowering action of syringin (100 microg/kg, i.v.) was observed in conscious rats with alpha1-adrenoceptor blockade by prazosin. The stimulatory actions of syringin on the secretion of plasma insulin and C-peptide were also obtained in prazosin-treated conscious rats. The obtained results suggest that insulinotropic effect of syringin on the plasma glucose regulation is impaired in conscious rats with a regular sympathetic tone; decrease of sympathetic tone as observed in anesthetized animal might be helpful in the therapeutic benefit of syringin.     

The calpain system and diabetes

Diabetes mellitus is recognized as a clinical syndrome that is characterized by hyperglycemia due to deficiency of insulin. The global prevalence of diabetes has been estimated to increase from 4% (1995) to 5.4% by the year 2025. Insulin dependent diabetes mellitus (IDDM/Type-1) in human, generating hyperglycemia due to insulin deficiency as a consequence of destructing beta cells in the pancreatic islets. Non-insulin dependent diabetes mellitus (NIDDM/Type-II), is a multifactorial, exact biochemical and genetic defect which has not yet been elucidated completely. Calpains seem to play a role in NIDDM and IDDM. Positional cloning experiments revealed that there is a NIDDM susceptibility to calpain 10 (CAPN10). Increased calpain activity and leukocyte trafficking were noticed in the microcirculation in ZDF (Zuker diabetic fatty) rats. Exercise and low body weight play a significant role in reducing calpains expression or elevating the calpains degradation in the skeletal muscle of NIDDM rats. Numerous investigations have been reported that non-coding polymorphisms in CAPN10 proteins might be involved in the NIDDM. Calpain and its mRNA presence had been reported in tissues from many mammalian species. CAPN10 and other calpains seem to be linked to glucose metabolism, insulin secretion and action pathways. This review will give an overview of the role of calpain in NIDDM and IDDM.