Trying times for human insulin.

The introduction of human insulin to treat diabetics seemed straightforward. What can account for the problems that have followed?     

Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by a paucity of adipose (fat) tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperinsulinaemia, hyperglycaemia and enlarged fatty liver. We have developed a mouse model that mimics these features of CGL: the syndrome occurs in transgenic mice expressing a truncated version of a nuclear protein known as nSREBP-1c (for sterol-regulatory-element-binding protein-1c) under the control of the adipose-specific aP2 enhancer. Adipose tissue from these mice was markedly deficient in messenger RNAs encoding several fat-specific proteins, including leptin, a fat-derived hormone that regulates food intake and energy metabolism. Here we show that insulin resistance in our lipodystrophic mice can be overcome by a continuous systemic infusion of low doses of recombinant leptin, an effect that is not mimicked by chronic food restriction. Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.     

重组人胰岛素的体外复性纯化

对大肠杆菌表达的重组人胰岛素原包涵体蛋白的变性复性条件进行了优化。考察了变性液中DTT的浓度,复性液的pH值,还原型谷胱甘肽(GSH)与氧化型谷胱甘肽(GSSG)的物质的量比,甘氨酸(Gly)浓度对复性的影响。结果表明,在变性液中加入60mmol/L DTT,复性液pH9.5,GSH与GSSG物质的量比为5∶1,Gly浓度为50mmol/L条件下复性率最高。复性后的重组人胰岛素原过DEAE-Sepharose FF柱,经过TPCK-胰蛋白酶和羧肽酶B酶切后,再过Sephadex G-25柱,得到纯度较高的重组人胰岛素。目的蛋白收率为96mg/g干菌体。     

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.     

Sequence of the human insulin gene

The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences.     

Autoantibodies to the insulin receptor in juvenile onset insulin-dependent diabetes

Insulin-dependent diabetes mellitus (IDDM) usually begins in childhood or early adulthood, and its aetiology is thought to involve autoimmune damage to the islet cells that secrete insulin. To investigate an additional target of autoimmunity in IDDM we examined sera for antibodies to insulin receptors. Such antibodies were defined by their ability to compete with insulin for binding to insulin receptors and by their capacity to behave like insulin in activating lipogenesis in adipocytes. We now report the occurrence of anti-insulin receptor antibodies of the IgM class in the sera of 10 of 22 IDDM patients obtained before their treatment with exogenous insulin. Furthermore, two of five IDDM patients who were initially negative developed anti-insulin receptor antibodies during treatment with human or pork insulin. These findings suggest that autoimmunity to the insulin receptor may contribute to the pathophysiology of IDDM.     

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.     

基于半监督学习的人体异常行为识别

需要进行人体异常行为识别的视频一般都是未标记的序列图像,传统的有监督的识别方法往往不能较好地反映其行为的特征,识别率不高.提出了一种基于半监督学习的人体异常行为识别方法,首先使用基于DTW距离的self-training进行标记数据扩充,然后用此扩充的序列图像样本集合训练对应的HMM,最终进行异常行为识别.实验结果证明该方法有效且识别率较高.     

Mapping of mutation causing Friedreich's ataxia to human chromosome 9

Friedreich's ataxia is an autosomal recessive disease with progressive degeneration of the central and peripheral nervous system. The biochemical abnormality underlying the disorder has not been identified. Prompted by the success in localizing the mutations causing Duchenne muscular dystrophy, Huntington's disease and cystic fibrosis, we have undertaken molecular genetic linkage studies to determine the chromosomal site of the Friedreich's ataxia mutation as an initial step towards the isolation and characterization of the defective gene. We report the assignment of the gene mutation for this disorder to chromosome 9p22-CEN by genetic linkage to an anonymous DNA marker MCT112 and the interferon-beta gene probe. In contrast to the clinical variation seen for the disorder, no evidence of genetic heterogeneity is observed.