Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.     

回肠转位手术对猪血糖及肠激素的调节作用

的探讨回肠转位手术对猪血糖代谢的调节作用、肠激素水平及体质量的影响。方法将19只Yorkshire猪按随机数字表法分为回肠转位手术组（10只）及手术对照组（9只），分别实施回肠转位手术及对照手术。术前及术后1～4周，每周测定体质量；术前、术后2周、术后4周静脉采血检测WBC、RBC、红细胞压积（HCT）、Hb等实验室生化指标；术前、术后第4周经十二指肠灌注行葡萄糖耐量实验（DGTT），记录各时相点血糖值，绘制曲线并计算曲线下面积；DGTT中，分别采集0min和40min静脉血样检测血清胰高血糖素样肽1（GLP一1）。实验数据采用Mann—WhitneyU非参数检验。结果回肠转位手术组和手术对照组Yorkshire猪术后1、2、3、4周体质量分别为29．5、30．3、31．6、32．1kg和26．1、28．9、30．5、34．1奴，两组Yorkshire猪术后2、3、4周体质量均分别较术后1周有明显增长（Z日肠转位手糊=2．11，2．21，2．33，Z手术枷目=2．13，2．18，2．27，P〈0．05）；术后4周两组Yorkshire猪体质量比较，差异无统计学意义（Z=0．45，P〉0．05）。回肠转位手术组Yorkshire猪术后2周和4周WBC、RBC、HCT、Hb分别为（19．9±3．2）x10’儿、（5．40±0．21）×10μg/L、（29．8±1．4）×10μg/L、（84±4）g／L和（23．3±2．5）×10μg/L、（5．30±0．22）X10μg/L、（30．1±1．6）×10μg/L、（85±4）g／L，术前分另0为（16．7±1．6）×10μg/L、（5．80±0．22）×10μg/L、（33．1±1．3）×10μg/L、（92±4）g／L，术后与术前各指标比较，差异无统计学意义（Zw。。=1．24，1．54，ZR=0．84，0．88，zHcT=0．95，0．83，ZHb=1．25，1．17，P〉0．05）；手术对照组Yorkshire猪术后2周和4周上述指标分别为（18．7±2．3）X10μg/L、（5．50±0．21）×10μg/L、（33．3±1．1）×10μg/L、（89±4）g／L和（16．2±0．7）×10μg/L、（5．60±0．16）×10”／L、（34．5±1．6）X10μg/L、（89±4）g／L，与术前相应指标（检测值同回肠转位手术组术前指标）比较，差异无统计意义（ZwBc=1．04，0．36，ZRBc=0．78，0．43，ZHcT=0．22，0．42，ZHb=0．78，0．79，P〉0．05）。回肠转位手术组Yorkshire猪血糖峰值为（10．6±2．9）mmol／L，较术前的（13．5±2．6）mmol／L和手术对照组的（13．3±3．7）mmol／L显著降低（Z：2．31，2．30，P〈0．05）；回肠转位手术组Yorkshire猪血糖达峰值时间为（90±11）min，较手术对照组的（50±5）min明显延迟（Z=2．29，P〈0．05）；回肠转位手术组Yorkshire猪糖耐量曲线下面积为（1569±546）mmol／LXrain，明显低于术前基线水平（1938±873）nmlol／LXmin（z：2．26，P〈0．05）。术后第4周，葡萄糖灌注后40rain回肠转位手术组Yorkshire猪血浆GLP-1水平为（10．0±1．6）斗∥L，明显高于手术对照组的（4．3±1．7）μg/L（z=2．12，P〈0．05）。结论在Yorkshire猪大型哺乳类动物模型中，回肠转位手术可以有效改善其血糖代谢，并伴有肠激素GLP一1水平的升高，且手术本身并不导致机体体质量的下降。     

糖脉康联合门冬胰岛素30对2型糖尿病患者血糖漂移及低血糖发生率的影响

目的用动态血糖监测方法评价糖脉康颗粒联合门冬胰岛素30注射液治疗2型糖尿病时对患者血糖漂移及低血糖发生率的影响。方法选取64例2型糖尿病患者,随机分为观察组和对照组,各32例。两组均给予2次/d门冬胰岛素30注射液皮下注射,观察组另联合糖脉康颗粒3次/d口服。采用动态血糖监测的方法,评价两组患者血糖漂移幅度、日胰岛素用量及低血糖发生情况。结果血糖达标持续3个月后,观察组患者的日均胰岛素用量〔(28.6±7.4)U/d〕、日内血糖最高值〔(13.1±1.2)mmol/L〕、平均血糖漂移幅度〔(7.4±1.2)mmol/L〕均显著低于对照组〔分别为(35.4±5.2)U/d、(16.2±1.6)mmol/L、(8.4±1.7)mmol/L〕,差异有统计学意义(P<0.05);另外,观察组患者发生低血糖7人次(5例),对照组5人次(4例),两组患者低血糖发生率(15.6%与12.5%)比较,差异无统计学意义(P>0.05)。结论在血糖控制达标时,与单用门冬胰岛素30注射液比较,糖脉康颗粒联合门冬胰岛素30注射液治疗能降低2型糖尿病患者的血糖漂移幅度及日均胰岛素用量,且不增加低血糖发生率。     

抗阻力运动对2型糖尿病患者糖耐量试验后自主神经功能紊乱的影响

目的 观察12周渐进抗阻力运动对2型糖尿病（T2DM）患者空腹时以及口服葡萄糖耐量试验（OGTT）后自主神经功能的影响并探讨其可能作用机制。 方法 采用随机数字表法按3∶2比例将50例T2DM患者分为运动组（30例）及对照组（20例）。2组患者均保持日常生活习惯不变,运动组患者在此基础上给予12周渐进抗阻力运动。于干预前、干预12周后测定2组患者血糖控制参数［包括血糖、血胰岛素、糖化血红蛋白以及胰岛素抵抗指数(IRI)等］以及空腹和OGTT后自主神经功能参数（如心率变异性、血压变异性和压力反射敏感性等）。 结果 干预后运动组患者空腹血糖控制参数（血胰岛素除外）均明显低于干预前水平（P<0.05）,而自主神经功能参数较干预前无明显改变（P>0.05）;干预后运动组患者OGTT时自主神经功能参数总功率（LnTP）、低频功率(LFn)、LnLF/高频功率（HF）和LFSBP均较干预前明显增加（P<0.05）;对照组干预后上述各项指标均无明显改变（P>0.05）。组间比较发现,干预后运动组患者血糖控制参数（血胰岛素除外）均显著低于对照组水平（P<0.05）,2组患者空腹时自主神经功能各参数组间差异均无统计学意义（P>0.05）,OGTT后运动组LnTP、LFn、LnLF/HF和LFSBP均显著高于对照组水平（P<0.05）。通过相关分析发现,运动组患者△LnLF/HF与△IRI（r＝-0.469,P<0.05）具有负相关性。 结论 12周渐进抗阻力运动虽然对T2DM患者空腹时自主神经功能无明显影响,但能增强OGTT后心交感和交感缩血管神经调制,其作用机制可能与抗阻力运动诱导的胰岛素抵抗减轻有关。     

老年2型糖尿病患者血糖控制全面评估

目的对老年2型糖尿病患者血糖控制情况进行全面评估,并探讨糖化血红蛋白（HbAlc）与血糖波动的相关性;方法选取老年糖尿病患者共284名,测定空腹血糖（FPG）、餐后2h血糖（PPG）、HbAlc水平,进一步采用动态血糖监测系统（CGMS）评估血糖波动情况。按照HbAlc水平分为两组（HbAlc≤7％组和HbAlc〈7％组）,比较两组间血糖控制水平及血糖波动情况。结果本研究中老年糖尿病患者FPG达标率为67．6％,PPG为34．9％,HbAlc为42．9％,血糖波动正常范围内的患者占28．6％,血糖波动大的患者占71．4％。两组间比较,FPG、PPG、MBG差异有统计学意义（P〈0．01）;但两组间代表血糖波动的各参数平均血糖标准差（SDBG）、最大血糖波动幅度（LAGE）、平均血糖波动幅度（MAGE）、日间血糖波动幅度（MODD）相比,差异无统计学意义（P〉0．05）。相关性分析表明,MAGE及MODD均与HbAlc水平无关（P〉0．05）。结论大多数老年糖尿病患者的血糖控制未达标,且约70％的老年糖尿病患者血糖波动大。HbAlc与血糖波动无关,HbAlc和血糖波动是评价血糖控制的独立指标。     

Practical implementation of incretin-based therapy in hospitalized patients with type 2 diabetes

Hyperglycemia in patients with and without a prior history of diabetes is an independent marker of morbidity and mortality in critically and noncritically ill patients. Improvement of glycemic control with insulin therapy has been shown to reduce hospital complications in patients with diabetes, but also results in increased rates of hypoglycemia, which have been linked to poor outcomes. Thus, alternative treatment options that can normalize blood glucose levels without undue hypoglycemia are being sought. Incretin-based therapies, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, stimulate insulin secretion in a glucose-dependent fashion, thus not causing hypoglycemia. Alternative points of view exist regarding insulin versus incretin therapy for the care of these patients. We have brought together the authors on the opposite sides of this discussion with the objective of providing a rational synthesis on how to achieve the best possible control of glycemia in the hospital, using both standard insulin approaches and incretin-based therapies to improve patient outcomes. This review examines the benefits of incretin-based therapy in improving glycemic control in hospitalized patients with stress-induced diabetes and in diabetic patients in critical care and non–critical care settings.     

Preterm delivery in normoalbuminuric, diabetic women without preeclampsia: the role of metabolic control

OBJECTIVE: The aim of this study was to examine the importance of glycemic regulation on the risk of preterm delivery in women with normoalbuminuria and no preeclampsia later in pregnancy. STUDY DESIGN AND METHODS: A prospective study of 71 women with type 1 diabetes mellitus where complete data were collected on HbA1c, insulin dose, and albumin excretion rate from week 12 and every second week hereafter. Fundus photography was performed and diurnal blood pressure measured three times during pregnancy. RESULTS: The preterm rate was 23% and women delivering preterm showed higher HbA1c throughout pregnancy. At regression analysis HbA1c was the strongest predictor for preterm delivery from week 6 to 32, also when including insulin dose, BMI, age, duration of diabetes, and diurnal blood pressure. The risk of delivering preterm was more than 40% when HbA1c was above 7.7% in week 8. Diurnal blood pressure was not found associated with preterm delivery. CONCLUSION: The quality of glycemic regulation in the early and mid-pregnancy is a major, independent risk factor for preterm delivery in normoalbuminuric diabetic women without preeclampsia.