基于“毒邪”理论的调控自噬对2型糖尿病的干预

糖尿病(DM)是一种在世界上普遍存在的慢性非传染性疾病。中国DM患者人数居世界首位。据估计,到2045年,中国DM患者将超过1.497亿。因此,开展中医药防治DM机制研究具有重要意义。现代医学目前研究表明,自噬是细胞对内环境变化的有效反应,是细胞的自我保护机制,在实现细胞的自我净化、自我重构、维持内环境稳态等方面起着不可替代的重要作用,此外,最近的研究发现自噬调节失衡参与2型DM(T2DM)发生发展过程并起着至关重要的作用〔1~4〕。T2DM的发病机制较为复杂,其中两个关键环节是胰岛素抵抗和胰岛β细胞衰竭。研究发现自噬作为一种保护机制在细胞稳态平衡中起着重要的调节作用,在T2DM的发展进程中,自噬可根据机体所处内环境不同被代偿性激活或被抑制,并且还发现当自噬调节不平衡时,胰岛素抵抗和胰岛β细胞衰竭进一步加重。     

从改善脂肪组织炎症方面探讨推拿手法治疗肥胖2型糖尿病胰岛素抵抗机制

糖尿病(DM)因其发病率、死亡率、致残率高而严重危害人类健康.其中肥胖的2型DM(T2DM)发病率逐年提高,肥胖的T2DM普遍存在胰岛素抵抗(IR),可并发多种并发症.因此,长期以来,T2DM IR的发病机制及治疗是人们的研究热点.     

肠道菌群代谢产物与胰岛素抵抗相关衰老疾病的研究进展

2型糖尿病(T2DM)和阿尔茨海默病(AD)都是与年龄相关的衰老性疾病,二者存在多种共同危险因素.肠道微生物通过多种代谢产物参与胰岛素生理机能的调控过程,在胰岛素抵抗(IR)发生发展中发挥重要的作用.该文从IR的角度,对肠道菌群代谢产物与T2DM及AD发病机制的内在联系作一综述.     

糖尿病患者正常糖耐量一级亲属脂联素、瘦素的变化

胰岛素抵抗(IR)和胰岛素分泌不足是2型糖尿病(T2DM)的重要发病机制,IR是预测T2DM发生的独立危险因素。大量研究发现脂联素、瘦素参与了T2DM IR的发生和发展〔1〕。T2DM患者一级亲属IR程度显著高于无家族史者,脂联素与瘦素联合影响T2DM患者一级亲属的IR程度〔2〕。因此我们测定T2DM正常糖耐量一级亲属(NFDR)血清脂联素、瘦素水平,以进一步探讨NFDR脂联素、瘦素的变化及与IR的关系。1对象与方法1.1对象以T2DM患者NFDR60例为NFDR组,男27例,女33例,年龄38~62(平均42±7)岁,体重指数(BMI)(24.7±3.2)kg/m2,同时选择同期无糖…     

南昌地区2型糖尿病家系患者及一级亲胰岛素抵抗与体重指数等多因素相关性研究

2型糖尿病(T2DM)的发生有明显家族聚集倾向.国外报道T2DM患者的后代约30%～40%将患T2DM[1].大多数T2DM患者在其病程中存在胰岛素抵抗(IR)和胰岛细胞功能异常与不足两方面的问题,但哪一项是首要发病机制则尚有争议[2,3],他们是遗传缺陷和环境因素共同作用的结果.本组在对T2DM的家系调查中研究了部分DM患者及其一级亲:包括正常糖耐量(NGT),糖耐量异常(IGT)/空腹血糖受损(IFG),及新发现DM者,胰岛素抵抗(IR)及其与年龄、血压(BP)、体重指数(BMI)、腰臀比(WHR)、血脂、血糖(BG)、胰岛素(INS)等参数的关系,以探讨其临床意义.     

2型糖尿病与炎症及抗炎疗法

在2型糖尿病(Type 2 diabetes mellitus,T2DM)的发病机制中,胰岛素抵抗(Insulin resistence,IR)和胰岛β细胞功能障碍是两个重要环节.虽然其确切的发病机制尚未完全阐明,但越来越多的证据提示T2DM及其并发症的发生同炎症密切相关,T2DM是一种自然免疫和慢性亚临床炎症疾病;而且抗炎治疗可以改善T2DM患者糖代谢异常、提高胰岛素敏感性,祖国中医也逐渐显示出其重要作用.     

2型糖尿病与8羟基脱氧鸟苷

2型糖尿病(T2DM)的发病机制主要为胰岛素抵抗(IR)及β细胞功能受损两方面,目前认为只有IR不足以引发DM而需同时有β细胞功能受损,IR为始动因子,β细胞功能异常为决定因子.近年来的研究认为胰岛β细胞是一个氧化应激易受损害的器官,与T2DM的β细胞功能进行性减退有关,高糖毒性及脂毒性在T2DM的发生发展过程中均起到重要作用,高糖毒性及脂毒性均与氧化应激有关,高血糖致使活性氧簇ROS增加,大大超过了机体的清除能力,ROS蓄积并导致氧化应激的发生,可引起β细胞凋亡及抑制胰岛素合成,降低外周组织对胰岛素的敏感性,导致DM的发生.     

炎症与胰岛素抵抗

胰岛素抵抗(IR)是发生代谢综合征(MS)、2型糖尿病(T2DM)和动脉粥样硬化(AS)的主要病理生理学改变之一，其传统的定义是胰岛素维持正常血糖的能力下降，主要发生在肝、骨骼肌和脂肪组织。虽然从胰岛素基因编码到葡萄糖代谢的过程中的任何步骤出现异常均可发生IR，但对于绝大多数肥胖或T2DM患者，发生IR的分子机制是靶细胞胰岛素受体后信号传导通路的缺陷[Pickup JC，eta1．Diabetes Care，2004，813]。     

2型糖尿病患者血管生成素样蛋白3水平变化及与胰岛素抵抗的关系

选择69例2型糖尿病(T2DM)患者(T2DM组)和15例健康查体者(对照组),测定其血清血管生成素样蛋白3(ANGPTL3)水平.计算胰岛素抵抗(IR)指数(HOMA-IR),并分析二者的相关性.结果 T2DM组血清ANGPTL3水平明显高于对照组(P＜0.01);T2DM组肥胖者的血清ANGPTL3 IR水平与HOMA-IR呈正相关.认为ANGPTL3与T2DM患者IR密切相关,在12DM发生和发展中起重要作用.     

三酰甘油-葡萄糖指数与2型糖尿病及其并发症的关系研究进展

综述三酰甘油-葡萄糖(TyG)指数与2型糖尿病(T2DM)及其并发症的关系。胰岛素抵抗(IR)是T2DM的主要发病机制,早期识别IR对于预测及预防T2DM的发病、延缓疾病进展具有重要意义。TyG指数可作为IR的替代指标,且其与T2DM及其并发症存在不同程度的关系。     

自噬与2型糖尿病

自噬是机体处于物质与能量代谢障碍时主要防御机制之一,在维持胰岛β细胞结构功能、改善IR等方面有重要作用。某些治疗T2DM药物也参与自噬途径调节。本文就近年关于自噬对T2DM影响的相关研究进行综述。     

The role of autophagy in insulin resistance and glucolipid metabolism and potential use of autophagy modulating natural products in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a severe, long-term condition characterised by disruptions in glucolipid and energy metabolism. Autophagy, a fundamental cellular process, serves as a guardian of cellular health by recycling and renewing cellular components. To gain a comprehensive understanding of the vital role that autophagy plays in T2DM, we conducted an extensive search for high-quality publications across databases such as Web of Science, PubMed, Google Scholar, and SciFinder and used keywords like ‘autophagy’, ‘insulin resistance’, and ‘type 2 diabetes mellitus’, both individually and in combinations. A large body of evidence underscores the significance of activating autophagy in alleviating T2DM symptoms. An enhanced autophagic activity, either by activating the adenosine monophosphate-activated protein kinase and sirtuin-1 signalling pathways or inhibiting the mechanistic target of rapamycin complex 1 signalling pathway, can effectively improve insulin resistance and balance glucolipid metabolism in key tissues like the hypothalamus, skeletal muscle, liver, and adipose tissue. Furthermore, autophagy can increase β-cell mass and functionality in the pancreas. This review provides a narrative summary of autophagy regulation with an emphasis on the intricate connection between autophagy and T2DM symptoms. It also discusses the therapeutic potentials of natural products with autophagy activation properties for the treatment of T2DM conditions. Our findings suggest that autophagy activation represents an innovative approach of treating T2DM.     

Insulin resistance and metabolic syndrome in type 1 diabetes mellitus

Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40% in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.     

IGF-1 contributes to liver cancer development in diabetes patients by promoting autophagy

Introduction and objectivesType 2 diabetes mellitus (T2DM) increases the occurrence and mortality of liver cancer. Insulin growth factor (IGF) plays a crucial role in the development of diabetes and liver cancer, and specifically, IGF-1 may be involved in the development of liver cancer with preexisting T2DM. Autophagy contributes to cancer cell survival and apoptosis. However, the relationship between IGF-1 and autophagy has rarely been evaluated. The purpose of this study was to investigate whether IGF-1 promotes the development of liver cancer in T2DM patients by promoting autophagy.Materials and methodsThirty-three hepatocellular carcinoma (HCC) patients with T2DM and 33 age-matched patients with HCC without T2DM were included in this study. We analyzed the expression of IGF-1 and autophagy-related LC3 and p62 mRNA and the prognosis of two groups. In vitro, we stimulated HepG2 cells with IGF-1 and then detected changes in autophagy and cell proliferation, apoptosis, and migration in the presence/absence of wortmannin, an autophagy inhibitor.ResultsIGF-1 promoted autophagy, resulting in inhibition of apoptosis and induction of growth and migration of HepG2 cells. Inhibition of autophagy by wortmannin impaired IGF-1 function. Higher expression of IGF-1 was detected in HCC patients with T2DM. IGF-1 expression was higher in liver cancer tissue compared to paracancerous tissue. Elevated IGF-1 was associated with a poor prognosis in patients with HCC.ConclusionsIGF-1 participates in the development of liver cancer by inducing autophagy. Elevated IGF-1 was a prognostic factor for patients with HCC, especially when accompanied by T2DM.     

2型糖尿病患者血浆Apelin-12水平与高血压、胰岛素抵抗的相关性

目的探讨Apelin-12与高血压、肥胖、胰岛素抵抗、炎症等的相关性。方法测定31例单纯2型糖尿病、37例2型糖尿病合并高血压患者及25例健康对照者血浆Apelin-12、肿瘤坏死因子α(TNF-α)、血脂、糖化血红蛋白(HbA1c)、空腹血糖、空腹胰岛素(FINS)、胰岛素抵抗(IR)指数(HOMA-IR)、体重指数(BMI)、血压等水平并进行各参数之间的相关分析。结果①糖尿病合并高血压组血浆Apelin-12水平低于正常对照组和单纯糖尿病组(P0.05或P0.01),单纯糖尿病组血浆Apelin-12水平高于正常对照组(P0.05)。②糖尿病合并高血压组TNF-α水平高于糖尿病组和正常对照组(P0.05或P0.01),糖尿病组TNF-α水平高于正常对照组(P0.05)③直线相关分析显示,空腹血浆Apelin-12与腰臀比(WHR),FINS,HOMA-IR,甘油三酯(TG),收缩压(SBP),TNF-α呈负相关,与HDL-C呈正相关。结论血浆Apelin-12水平在糖尿病组升高,在糖尿病合并高血压组降低,且与肥胖、IR、炎症等相关。推测Apelin-12可能参与了IR、2型糖尿病、高血压等疾病的发生发展。     

2型糖尿病患者性激素水平与胰岛素抵抗的关系

目的 研究2型糖尿病(T2DM)患者性激素水平与胰岛素(INS)、胰岛素抵抗(IR)、胰岛素敏感性的关系。方法 对63例T2DM患者(男35例,女28例)以及正常对照组45例(男24例,女21例),用放免法测定雌二醇(E_2)和睾酮(T),用酶联免疫测定法测定INS,计算IR和胰岛素敏感指数(ISI)并进行比较。结果 T2DM患者存在性激素紊乱。女性DM组E_2与INS、IR呈负相关(分别是r=-0 38,P<0.05,r=-0.42,P<0.05),与ISI呈正相关(r=0.53,P<0.01);T与INS、IR呈正相关(分别是r=0.48,P<0.01;r=0.74,P<0.01);与ISI呈负相关(r=-0.77,P<0.01)。男性DM组,E_2与INS呈正相关(r=0.36,P<0.05);T与INS、IR呈负相关(分别是r=-0.37,P<0.05;r=-0.47,P相似文献   

Etiology of Insulin Resistance in Youth with Type 2 Diabetes

Type 2 diabetes (T2DM), historically an adult disease, is now increasingly prevalent in obese youth. Poor diet and increased sedentary behavior contribute to the increasing rates of obesity in youth, yet not all obese children develop T2DM. In general, T2DM is characterized by both insulin resistance (IR) and pancreatic beta-cell insufficiency. In children, IR is related to elevated body mass index (BMI) and pubertal hormones, along with abnormal fat partitioning, elevated free fatty acids, inflammation, and/or mitochondrial dysfunction. Hyperglycemia and T2DM develop when the pancreas cannot match the increased insulin demands resulting from IR. Unique to youth, IR varies with stage of pubertal development, and some children may have resolution of hyperglycemia post-puberty once the IR of puberty resolves. Further understanding of IR, the progression to T2DM in youth, and later outcomes as adults will help direct future therapies and interventions for youth at risk.     

Diabetic Foot Disease: Emerging Technologies: Repeatability of Infrared Plantar Thermography in Diabetes Patients: A Pilot Study

Objective

Infrared (IR) thermography has been used as a complementary diagnostic method in several pathologies, including distal diabetic neuropathy, by tests that induce thermoregulatory responses, but nothing is known about the repeatability of these tests. This study aimed to assess the repeatability of the rewarming index in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic control subjects.

Methods

Using an IR camera, plantar IR images were collected at baseline (pre-) and 10 min after (post-) cold stress testing on two different days with 7 days interval. Plantar absolute average temperatures pre- and post-cold stress testing, the difference between them (ΔT), and the rewarming index were obtained and compared between days. Repeatability of the rewarming index after the cold stress test was assessed by Bland–Altman plot limits of agreement.

Results

Ten T2DM subjects and ten nondiabetic subjects had both feet analyzed. Mean age did not differ between groups (p = .080). Absolute average temperatures of plantar region pre- (p = .033) and post-cold stress test (p = .019) differed between days in nondiabetic subjects, whereas they did not differ in T2DM subjects (pretest, p = .329; post-test, p = .540). ΔT and rewarming index did not differ between days for both groups, and the rewarming index presented a 100% agreement of day-to-day measurements from T2DM subjects and 95% with nondiabetic subjects.

Conclusions

The rewarming index after cold stress testing presented good repeatability between two days a week in both groups. Despite T2DM subjects presenting no differences on absolute temperature values between days, ΔT or rewarming index after cold stress testing remain recommended beside absolute temperature values for clinical use.     

非酒精性脂肪性肝病胰岛素抵抗程度与全血细胞计数的相关性

目的探讨伴或不伴2型糖尿病(T2DM)的非酒精性脂肪性肝病(NAFLD)胰岛素抵抗(IR)程度与全血细胞计数各参数的相关性。方法选取糖耐量正常并除外糖尿病史的单纯NAFLD患者102例,T2DM合并NAFLD患者104例,正常对照104例为研究对象,测定空腹血糖(FPG)、空腹胰岛素(FINS)和全血细胞计数,分析胰岛素抵抗指数(HOMA-IR)与全血细胞计数各参数的相关性。结果 T2DM合并NAFLD患者IR及全血细胞计数异常程度较单纯NAFLD患者更重;相关性研究表明男性HOMA-IR与WBC、NEU、LYM、RBC、HGB、HCT呈正相关,女性HOMA-IR与WBC、NEU、LYM、MID、RBC、HGB、HCT呈正相关。结论 NAFLD时白细胞参数和红细胞参数的变化与IR密切相关,T2DM的存在加重了IR对上述血细胞参数的影响。全血细胞计数可以作为反映NAFLD患者IR程度的一种简单实用的检验指标。     

胰岛素抵抗对2型糖尿病及单纯胰岛素抵抗老龄大鼠的肾损伤和骨密度的影响

目的观察胰岛素抵抗（IR）对2型糖尿病（T2DM）及单纯IR老龄大鼠的肾损伤和骨密度（BMD）的影响.方法18月龄Wistar大鼠30只,分为正常对照组、IR组、DM组,用正常血糖胰岛素钳夹技术（euglycemic insulin clamptechnique,EICT）测定各组大鼠IR,用葡萄糖输注速率（Glucoseinfusion rate,GIR）表示IR情况,放免法测定各组大鼠24 h尿白蛋白,双能X线骨密度测量仪（DEXA）测定各组大鼠腰椎、股骨BMD.结果DM组和IR组GIR低于N组（P＜0.01）.与对照组比较,DM组24h尿白蛋白升高（P=0.008）,IR组有升高趋势（P＞0.05）;DM组24 h尿白蛋白显著高于IR组（P=0.017 5）.IR组腰椎、股骨BMD低于正常对照组,高于DM组（P＜0.05）.IR组和DM组GIR与24 h尿白蛋白呈负相关,与腰椎、股骨BMD呈正相关.结论IR在T2DM及单纯IR时均可致肾脏损伤和骨密度降低.