地骨皮降血糖效果研究及成分分析

地骨皮为茄科落叶灌木枸杞的干燥根皮，多年来在中国民间被用于治疗肺炎、咳血、肢端坏疽及糖尿病等。本实验采用水提和醇提法分别对地骨皮有效成分进行提取，获得冻干粉。利用四氧嘧啶腹腔注射构建糖尿病模型，将实验鼠分为4组：正常对照组、糖尿病对照组、地骨皮低剂量组和高剂量组。将低、高剂量组小鼠每天分别灌胃100mg／kg，200mg／kg地骨皮水溶液，用药28天，每周监测血糖和体重变化，结果地骨皮处理组血糖水平与糖尿病阳性对照组比明显降低（p〈0．01），降低率达36．72％（低剂量组），41．89％（高剂量组）；体重与阳性对照组相比明显增加（P〈0．05）。第29天，取血测各组三脂酰甘油（TG）、胆固醇（TC）水平，结果与糖尿病对照组比二者均明显下降。再通过薄层色谱技术对地骨皮的各种成分进行鉴定，比较出两种提取方法上成分的差异，实验表明地骨皮具降糖作用，其主要成分是有机酸和生物碱类。     

中老年2型糖尿病患者糖尿病痛苦影响因素及对策的研究

目的 探讨中老年2型糖尿病患者糖尿病痛苦影响因素并总结相关对策实施效果。方法 抽取2020年1月~2020年6月井冈山大学附属医院收治的140名中老年2型糖尿病患者,使用中文版糖尿病痛苦量表（CDDS）评估本组患者糖尿病痛苦情况。同时本组患者接受正念训练,持续6个月后评估本组患者糖尿病痛苦量表与生活质量量表结果变化。结果 140例患者CDDS量表总分为（41.45±14.42）分,平均（2.55±0.86）分。患者性别、文化背景、家庭收入、病程长短、并发症等均存在统计学意义（P<0.05）。患者文化背景、病程长短是导致中老年2型糖尿病患者糖尿病痛苦的主要影响因素。持续6个月正念训练干预后本组患者CDDS量表得分相较干预前得分均有明显降低（P<0.05）。结论 文化背景与病程长短是导致中老年2型糖尿病患者糖尿病痛苦的主要影响因素,正念训练干预措施能有效缓解中老年2型糖尿病患者痛苦程度,具有积极价值。     

萘查耳酮类PTP1B抑制剂的合成与活性研究

蛋白酪氨酸磷酸酯酶1B(PTP1B)作为非受体型PTPase家族成员之一,参与很多生理和病理过程的调控,尤其是对胰岛素信号通路中能量和葡萄糖稳态的调控,使其成为治疗糖尿病和肥胖症的新靶点。本研究基于PTP1B活性位点,利用计算机辅助药物设计方法,设计、合成了一系列羟基萘查尔酮及其环合衍生物(1a-1g,2a-2g),并评估了它们对PTP1B酶的抑制活性。本研究获得了4个活性较好的PTP1B抑制剂,IC₅₀分别为1.91、8.59、7.38、4.64μM,为开发具有良好细胞渗透性和生物利用度的新型PTP1B抑制剂提供了新的方向。     

Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics. Received 3 May 2006; received after revision 9 June 2006; accepted 12 June 2006 Free Online Access     

Characterization of the Expression of CTRP9, a Paralog of Adiponectin

Adiponectin is one of the hormones secreted exclusively by the adipose tissue with anti-diabetic anti-inflammatory, anti-atherogenic, anti-atherosclerotic, and insulin-sensitizing effects. Adiponectin has structural features including a signal peptide at the N terminus, a short variable region, a collagenous domain, and a C-terminal globular domain homologous to Clq. The family of proteins containing this globular domain is called the C1q/tumor necrosis factor-a-related proteins （CTRP）. Among all the CTRPs characterized so far, the CTRP9 protein has the highest homology to adiponectin. However, little is known about the functions of CTRP9. This study examines the tissue expression of CTRP9 as well as the expression of CTRP9 during mouse development and 3T3-L1 preadipocyte differentiation. The effects of LPS, TNFα, and starvation on the expression of CTRP9 were also investigated. CTRP9 mRNA is shown to be expressed in a variety of tissues including the adipose tissues. The expression profile of CTRP9 differs from that of adiponectin, implying that they are functionally diverse although structurally homologous.     

Pyridoxamine as a multifunctional pharmaceutical: targeting pathogenic glycation and oxidative damage

The discovery that pyridoxamine (PM) can inhibit glycation reactions and the formation of advanced glycation end products (AGEs) stimulated new interest in this B₆ vitamer as a prospective pharmacological agent for treatment of complications of diabetes. The mechanism of action of PM includes: (i) inhibition of AGE formation by blocking oxidative degradation of the Amadori intermediate of the Maillard reaction; (ii) scavenging of toxic carbonyl products of glucose and lipid degradation; and (iii) trapping of reactive oxygen species. The combination of these multiple activities along with PM safety posture it as a promising drug candidate for treatment of diabetic complications as well as other multifactorial chronic conditions in which oxidative reactions and carbonyl compounds confer pathogenicity.Received 1 March 2005; received after revision 25 March 2005; accepted 31 March 2005     

Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells

The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations of interferon-γ, tumor necrosis factor-α, and IL-1β. The induction of iNOS by IL-17 was preceded by phosphorylation of p38 mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release. IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease. Received 14 June 2005; received after revision 17 September 2005; accepted 21 September 2005     

All in the family: aldose reductase and closely related aldo-keto reductases

Aldose reductase catalyzes the first step in the polyol pathway and is thought to be involved in the pathogenesis of diabetic complications. In addition to polyol synthesis, aldose reductase may have multiple other activities that intersect with signal processing and oxidative defense mechanisms. Multiple aldose reductase-like proteins have been discovered to have structures and catalytic properties that broadly overlap those of aldose reductase. This chapter will summarize new insights into properties and functions of aldose reductase and closely related members of the aldo-keto reductase enzyme superfamily.     

Role of glutamic acid decarboxylase in the pathogenesis of type 1 diabetes

Glutamic acid decarboxylase (GAD) is considered to be one of the strongest candidate autoantigens involved in triggering β-cell-specific autoimmunity. The majority of recent onset type 1 diabetes patients and prediabetic subjects have anti-GAD antibodies in their sera, as do nonobese diabetic (NOD) mice, one of the best animal models for human type 1 diabetes. Immunization of young NOD mice with GAD results in the prevention or delay of the disease as a result of tolerizing autoreactive T cells. Autoimmune diabetes can also be prevented by the suppression of GAD expression in antisense GAD trans genic mice backcrossed with NOD mice for seven generations. These results support the hypothesis that GAD plays an important role in the development of T-cell-mediated autoimmune diabetes. However, there is some controversy regarding the role of GAD in the pathogenesis of diabetes. Whether GAD truly plays a key role in the initiation of this disease remains to be determined. The examination of the development of insulitis and diabetes in β-cell-specific GAD knockout NOD mice will answer this remaining question. Received 12 April 2002; received after revision 24 May 2002; accepted 27 May 2002 RID="*" ID="*"Corresponding author.     

魔芋低聚糖降低糖尿病小鼠血糖和胆固醇效应的研究

主要研究魔芋低聚糖对实验性糖尿病小鼠血糖浓度的影响 .先用 5 %四氧嘧啶水溶液腹腔注射(ip)诱发小鼠糖尿病 ,再用不同剂量的魔芋低聚糖水溶液灌胃 (ig) ,先后测定小鼠血糖值及某些血液成分的含量 .实验 2周后结果显示 ,灌服了低、高剂量魔芋低聚糖液的糖尿病小鼠血糖值分别为 1 0 .4 1± 2 .2 3mmol L、9.81± 1 .67mmol L,与未用药的糖尿病组 (1 7.1 7± 3 .89mmol L)比较明显降低 (P <0 .0 1 ) ,同时血液中某些成分的含量改善 .提示魔芋低聚糖有明显的降血糖及改善血液成分的作用 ,为利用其开发降糖保健食品及药品提供了实验依据