Genetic analysis of autoimmune type 1 diabetes mellitus in mice.

Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17.     

2型糖尿病胰岛素抵抗研究进展

胰岛素抵抗和B细胞功能障碍是2型糖尿病发病机制的两个主要环节,而胰岛素抵抗是2型糖尿病发生的始动因素.研究发现,信号蛋白异常和炎症因子与胰岛素抵抗的发生密切相关,探讨其相关关系为治疗糖尿病、防治或延缓其并发症的发生提供重要的科学依据.     

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells - the cells that release insulin - failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.     

HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus

Over half of the inherited predisposition to insulin-dependent diabetes mellitus maps to the region of chromosome 6 that contains the highly polymorphic HLA class II genes which determine immune responsiveness. Analysis of DNA sequences from diabetics indicates that alleles of HLA-DQ beta determine both disease susceptibility and resistance, and that the structure of the DQ molecule, in particular residue 57 of the beta-chain, specifies the autoimmune response against the insulin-producing islet cells.     

Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.     

A structurally abnormal insulin causing human diabetes.

Insulin isolated from the pancreas of a diabetic patient with fasting hyperinsulinaemia showed decreased activity in binding to cell membrane insulin receptors and in stimulating cellular 2-deoxyglucose transport and glucose oxidation. Chemical studies suggest that the isolated hormone is a mixture of normal insulin and an abnormal variant which contains a leucine for phenylalanine substitution at position 24 or 25 of the insulin B-chain.     

运动对2型糖尿病胰岛素抵抗相关因子的影响研究

通过分析运动对2型糖尿病胰岛素抵抗的相关因子的影响,发现2型糖尿病主要是胰岛素抵抗和胰岛素分泌受损所导致.因此,只要了解胰腺β细胞的胰岛素抵抗程度,就可以加以弥补,使葡萄糖耐受性维持正常.     

Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice

A fundamental question about the pathogenesis of spontaneous autoimmune diabetes is whether there are primary autoantigens. For type 1 diabetes it is clear that multiple islet molecules are the target of autoimmunity in man and animal models. It is not clear whether any of the target molecules are essential for the destruction of islet beta cells. Here we show that the proinsulin/insulin molecules have a sequence that is a primary target of the autoimmunity that causes diabetes of the non-obese diabetic (NOD) mouse. We created insulin 1 and insulin 2 gene knockouts combined with a mutated proinsulin transgene (in which residue 16 on the B chain was changed to alanine) in NOD mice. This mutation abrogated the T-cell stimulation of a series of the major insulin autoreactive NOD T-cell clones. Female mice with only the altered insulin did not develop insulin autoantibodies, insulitis or autoimmune diabetes, in contrast with mice containing at least one copy of the native insulin gene. We suggest that proinsulin is a primary autoantigen of the NOD mouse, and speculate that organ-restricted autoimmune disorders with marked major histocompatibility complex (MHC) restriction of disease are likely to have specific primary autoantigens.     

长期口服家蚕生产的CTB-InsB融合蛋白对延缓NOD小鼠Ⅰ型糖尿病发作的研究

为对霍乱毒素B亚基(the cholera toxin B subunit,CTB)联合胰岛素B链（insulin B chain）表达的融合蛋白CTB-InsB长期口服延缓糖尿病发作的效果进行研究,将Ⅰ型糖尿病动物模型NOD小鼠随机分组,给予口服融合蛋白CTB-InsB后,检测尿糖、血糖,观测CTB-InsB对模型小鼠发病率的影响.试验表明与口服野生蚕血的对照组相比,每次口服融合蛋白CTB-InsB 50 μg对NOD小鼠糖尿病的发作具有明显延缓作用（P＜0.05）,而100 μg和10 μg的剂量虽有     

Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) which is characterized by an early age at onset and an autosomal dominant mode of inheritance. Except for these features, the clinical characteristics of patients with MODY are similar to those with the more common late-onset form(s) of NIDDM. Previously we observed tight linkage between DNA polymorphisms in the glucokinase gene on the short arm of chromosome 7 and NIDDM in a cohort of sixteen French families having MODY. Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Because the glucokinase gene was a candidate for the site of the genetic lesion in these families, we scanned this gene for mutations. Here we report the identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family. To our knowledge, this result is the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.     

胰岛素治疗糖尿病常见的护理问题与对策

目的探讨胰岛素治疗糖尿病常见护理问题及对策。方法对148例使用胰岛素治疗糖尿病住院患者加强常见护理问题的观察及处理。结果148例糖尿病患者在使用胰岛素治疗过程中未出现不良反应。结论加强对使用胰岛素治疗糖尿病患者常见问题的观察护理是保证糖尿病患者治疗成功的关键。     

胰岛素治疗糖尿病常见的护理问题与对策

目的 探讨胰岛素治疗糖尿病常见护理问题及对策.方法 对148例使用胰岛素治疗糖尿病住院患者加强常见护理问题的观察及处理.结果 148例糖尿病患者在使用胰岛素治疗过程中未出现不良反应.结论 加强对使用胰岛素治疗糖尿病患者常见问题的观察护理是保证糖尿病患者治疗成功的关键.