妊娠期糖尿病患者脂肪组织脂联素mRNA表达与胰岛素抵抗的关系

目的 探讨妊娠期糖尿病（GDM）患者脂肪组织脂联素mRNA表达与胰岛素抵抗（IR）的关系.方法 检测GDM患者（GDM组） 的皮下与网膜脂肪脂联素mRNA、血脂、空腹胰岛素（FINS）、游离脂肪酸（FFA）及胰岛素抵抗指数（HOMA-IR）等,并与正常孕妇（NGT组）和非育龄择期手术者（对照组）进行比较.结果 GDM组、NGT组和对照组的皮下脂肪脂联素mRNA表达均高于其网膜脂肪水平;对照组、NGT组、GDM组皮下、网膜脂肪脂联素mRNA表达依次降低（P均＜0.01）.三组TG、LDL-C、FFA、FINS 和HOMA-IR比较均有统计学差异（P均＜0.01）.GDM组网膜脂肪脂联素mRNA表达与CRP、FPG、FINS、HOMA-IR和孕前BMI等呈负相关（P＜0.01或＜0.05）.结论 GDM患者的网膜脂肪脂联素mRNA表达降低与其IR及GDM发生有关.     

脂联素与妊娠并发症的关系研究进展

脂联素(APN)是脂肪组织来源的血浆蛋白,具有调节胰岛素敏感性、抗动脉粥样硬化作用和抗炎症作用,参与胰岛素抵抗(IR)、血糖代谢的调节[1].人类妊娠存在生理性胰岛素抵抗,原因不明.研究表明妊娠期糖尿病(GDM)和子痫前期(PE)发病机制可能与APN代谢紊乱密切有关;APN作为胰岛素作用和血糖代谢的一个重要调节因子,对胎儿宫内发育有调节作用.现将APN与妊娠并发症的关系研究进展情况综述如下.     

妊娠糖尿病患者血清脂联素和TNF-α与胰岛素抵抗的关系

目的 探讨妊娠期糖尿病(GDM)患者血清脂联素和肿瘤坏死因子α(TNF-α)水平与胰岛素抵抗(IR)关系.方法 检测48例GDM患者(GDM组)、30例正常葡萄糖耐量妊娠者(NGT组)血清脂联素、TNF-α,分析两者与IR指数的相关性.结果 与NGT组比较,GDM组血清脂联素水平下降(P<0.01),TNF-α升高(P<0.01).脂联素与IR呈负相关(P<0.01),TNF-α与IR呈正相关(P<0.01).体质量指数(BMI)、脂联素和TNF-α是影响GDM患者IR的独立危险因素.结论 GDM患者血清低脂联素水平、高TNF-α水平与IR密切相关,是GDM发生发展的重要影响因素.     

精蛋白生物合成人胰岛素注射液联合饮食、运动干预对妊娠期糖尿病患者血糖控制及不良妊娠结局的影响

选取2019年3月-2020年6月我院GDM患者112例,随机平分为对照组采取饮食调节及运动干预、二甲双胍,研究组在对照组基础上采取精蛋白生物合成人胰岛素注射液。结果干预4周后两组FPG、2hPG水平较干预前降低,且研究组低于对照组(P<0.05);研究组血清瘦素、抵抗素、内脂素水平低于对照组,脂联素水平高于对照组(P<0.05);研究组不良妊娠结局发生率(8.93%)低于对照组(23.21%)(P<0.05)。结论联合采取精蛋白生物合成人胰岛素注射液、饮食调节、运动指导对GDM患者实施干预,可有效调控血糖,调节脂肪因子含量,降低不良妊娠结局发生风险。     

脂联素及其受体在酒精性肝病中的作用

脂联素是脂肪细胞特异分泌的一种脂肪因子,具有抗炎、促进脂肪酸氧化、减轻胰岛素抵抗等作用,在酒精性肝病患者及动物模型中,脂联素水平均下降,提示脂联素在酒精性肝病的发病中可能起重要作用,进一步研究其具体作用将为酒精性肝病的防治提供新的思路.     

妊娠糖尿病患者脂联素与胰岛素抵抗相关性的初步探讨

目的探讨妊娠糖尿病（GDM）患者脂联素与胰岛素抵抗（IR）的关系。方法检测40例GDM患者（GDM）、34例糖耐量正常（NGT）的孕妇作对照（NC）组的血清脂联素水平，同时以稳态模型HOMA-IR计算胰岛素抵抗指数。结果（1）GDM组脂联素水平、HOMA-IR分别为7．83±1．57μg／L，3．57±1．27，对照组分别为9．36±1．41μg／L、2．98±1．03，两组比较差异有统计学意义。（2）GDM组多元线性逐步回归分析结果显示孕前BMI、脂联素是影响GDM患者IR的独立危险因素。结论GDM患者血清脂联素减少与IR密切相关。     

西格列汀治疗对2型糖尿病患者胰岛素抵抗的影响

胰岛素抵抗是2型糖尿病(T2DM)发病的主要环节之一,但导致胰岛素抵抗的确切机制尚未阐明.近年来糖尿病研究中的重要进展之一是脂联素的发现,并且证实血清脂联素与胰岛素水平和胰岛素抵抗密切相关.西格列汀作为二肽基肽酶-4抑制剂,具有刺激胰岛β细胞再生,促进餐后胰岛素分泌,抑制内源性葡萄糖的生成,达到降低血糖的作用,同时能明显减重.本研究观察西格列汀治疗对T2DM患者胰岛素抵抗及血清脂联素水平的影响.     

运动与脂联素的关系及其在改善胰岛素抵抗中的作用

肥胖和胰岛素抵抗（IR）是引发糖尿病、高脂血症和动脉粥样硬化的主要危险因素。目前认为不良饮食习惯和缺乏适当的体育运动是肥胖和IR发生的主要原因。最新研究证明,脂肪组织不仅是机体能量的储存器,而且也是重要的内分泌器官,它可分泌大量的脂肪因子,这些脂肪因子通过对胰岛素、葡萄糖和脂肪代谢相关因子的调节,直接或间接的影响骨骼肌、肝赃等组织对胰岛素的敏感性。在众多脂肪组织分泌的脂肪因子中,脂联素因其具有抑制IR和糖尿病的作用而备受关注。有氧运动能够增加机体能量代谢,改善机体组织对胰岛素的敏感性,然而目前有氧运动对脂联素的影响尚不完全明确。本文对此领域研究现状加以综述。     

糖皮质激素诱导胰岛素抵抗的分子机制

糖皮质激素是体内重要的胰岛素拮抗激素,可诱导胰岛素抵抗。糖皮质激素可以干扰骨骼肌细胞的葡萄糖摄取和利用,抑制脂肪组织中葡萄糖转运蛋白（GLUT）-4的胞内分布及糖转运活性从而抑制糖摄取。并可通过调节脂肪细胞因子如脂联素、抵抗素、瘦素、内脏脂肪素的分泌,影响胰岛素的敏感性。此外,糖皮质激素还可抑制胰岛β细胞功能,使胰岛素分泌减少,并触发胰岛细胞凋亡。     

肿瘤坏死因子α、脂联素与非酒精性脂肪性肝病

非酒精性脂肪性肝病(NAFLD)包括单纯性脂肪肝,脂肪性肝炎、脂肪性肝硬化等,可能是生理(病理)的遗传环境下多种代谢失调的结果.目前认为,参与NAFLD发病机制的主要因素有:胰岛素抵抗(IR)、脂肪酸代谢紊乱、线粒体功能障碍、氧化应激、细胞因子失调和大量调节因子的产生.本文就肿瘤坏死因子α(TNF α)、脂联素在NAFLD发病中的作用及相互关系做一综述.     

New insights into the signaling system and function of insulin in fish

Fish have provided essential information about the structure, biosynthesis, evolution, and function of insulin (INS) as well as about the structure, evolution, and mechanism of action of insulin receptors (IR). INS, insulin-like growth factor (IGF)-1, and IGF-2 share a common ancestor; INS and a single IGF occur in Agnathans, whereas INS and distinct IGF-1 and IGF-2s appear in Chondrichthyes. Some but not all teleost fish possess multiple INS genes, but it is not clear if they arose from a common gene duplication event or from multiple separate gene duplications. INS is produced by the endocrine pancreas of fish as well as by several other tissues, including brain, pituitary, gastrointestinal tract, and adipose tissue. INS regulates various aspects of feeding, growth, development, and intermediary metabolism in fish. The actions of INS are mediated through the insulin receptor (IR), a member of the receptor tyrosine kinase family. IRs are widely distributed in peripheral tissues of fish, and multiple IR subtypes that derive from distinct mRNAs have been described. The IRs of fish link to several cellular effector systems, including the ERK and IRS-PI3k-Akt pathways. The diverse effects of INS can be modulated by altering the production and release of INS as well as by adjusting the production/surface expression of IR. The diverse actions of INS in fish as well as the diverse nature of the neural, hormonal, and environmental factors known to affect the INS signaling system reflects the various life history patterns that have evolved to enable fish to occupy a wide range of aquatic habitats.     

胰岛素治疗使糖尿病大鼠的胰岛素抵抗逆转

链脲佐菌素引起的糖尿病大鼠用胰岛素治疗6天后,治疗组(n=4)与未治疗组(n=20)比较:(1)体重和血清胰岛素浓度显著增加,而摄食量,饮水量和血糖均显著降低;(2)脂肪细胞膜胰岛素结合率显著降低,其胰岛素受体数目减少但受体亲和力没有改变;(3)基础(不加胰岛素时)和胰岛素刺激的脂肪细胞葡萄糖氧化均显著增加。提示胰岛素治疗虽使靶细胞上胰岛素受体数目减少,但可显著提高靶细胞对胰岛素的反应性,即可使受体后胰岛素抵抗减轻。     

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy

Aims/Introduction

To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.

Materials and Methods

In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.

Results

In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.

Conclusions

The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.     

Serum insulin,insulin antibodies and insulin requirement in the first period of insulin treatment in non-insulin resistant diabetics

Summary Twelve insulin-sensitive diabetics were studied for 200 days after the initiation of mixed beef-pork NPH insulin. Normalization of the fasting blood glucose was not accompanied by any elevation in the pre-treatment fasting immunoreactive insulin level. Insulin antibodies appeared in 2 patients on the second week of insulin treatment, in 6 others within 87 days. In 4 patients no antibodies were found 200 days after the start of insulin. The appearance of antibodies was accompanied in two patients by a decrease in insulin requirement, in others there was no change. When antibodies were present, the total maximum insulin binding capacity was 4 to 12 U/1, but the total insulin constituted only 3 to 36% of the binding capacity. Insulin wastage caused by the destruction of the immune complexes was calculated to be 0.35 to 5.6 U/die only, and this explains the negligible effect of insulin antibodies on insulin requirement in non-resistant patients. Presented at the 10th Annual Meeting of the European Association for the Study of Diabetes in Jerusalem, September 11–13, 1974.     

Insulin-derived Amyloidosis and Poor Glycemic Control: A Case Series

Objectives

Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption.

Methods

Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients.

Results

When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030).

Conclusions

Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.     

Semantics of insulin

The lack of a stringent terminology and a well-defined vocabulary for insulin and related subjects has been a deterrent to solving many of the problems encountered when using insulin in pumps. The same word is sometimes used to describe a number of different phenomena or the same phenomenon is referred to by different words. Thus the word 'insulin', meaning the substance, the protein hormone, is commonly used as a synonym for an 'insulin formulation' for the treatment of diabetes. The 'insulin dimer' can be the covalent or the non-covalent dimer, two very different substances. 'Isoelectric precipitation' is often mistaken for 'fibrillation' and both are referred to as 'aggregation' or 'polymerization'. The word 'crystal' is being used as a synonym for 'particle', and determination of 'the content of insulin' by HPLC is sometimes called a 'bioassay'. The nature and consequences of these pitfalls are discussed, and advice is given on how to avoid them.     

胰岛素的糖基化作用及其与胰岛素抵抗的关系

人胰岛素在体外与不同浓度葡萄糖溶液孵育，利用氯化硝基四唑氮蓝还原反应证实胰岛素能被糖基化；利用抗胰岛素抗体分离３３例Ⅱ型糖尿病患者血清胰岛素，比色测定糖基化胰岛素水平。结果表明：糖尿病患者糖基化胰岛素水平显著升高，且与血糖呈显著正相关，与空腹血胰岛素／血糖比值和糖负荷后曲线下胰岛素／血糖面积比值呈显著负相关。说明糖基化胰岛素水平取决于血糖控制状况。且可能参与胰岛素抵抗的形成。     

链脲佐菌素糖尿病大鼠的胰岛素受体结合、胰岛素介体释放和葡萄糖氧化

作者测定了链脲佐菌素引起的糖尿病大鼠脂肪细胞膜对胰岛素特异结合率、肝细胞膜胰岛素介体释放和脂肪细胞葡萄糖氧化。结果表明:(1)糖尿病大鼠脂肪细胞膜对胰岛素特异结合率较正常大鼠显著增加,其胰岛素受体亲和力没有改变,但受体数目增加;(2)大鼠肝细胞膜加胰岛素诱导时,糖尿病鼠肝膜释放的抑制腺苷酸环化酶活力的胰岛素介体量较正常大鼠显著减少;(3)在糖尿病大鼠,基础的和胰岛素刺激的脂肪细胞葡萄糖氧化较正常大鼠显著降低。提示胰岛素介体释放量减少可能是引起受体后胰岛素抵抗的原因之一。