共查询到20条相似文献，搜索用时 31 毫秒
1.
Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor 总被引：11，自引：0，他引：11
M Taira M Taira N Hashimoto F Shimada Y Suzuki A Kanatsuka F Nakamura Y Ebina M Tatibana H Makino 《Science (New York, N.Y.)》1989,245(4913):63-66
The insulin receptor has an intrinsic tyrosine kinase activity that is essential for signal transduction. A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans. Insulin binding to the erythrocytes or cultured fibroblasts from this individual was normal. However receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the proband's lymphocytes that had been transformed by Epstein-Barr virus. The insulin resistance associated with this mutated gene was inherited by the proband from her mother as an apparently autosomal dominant trait. Thus a deletion in one allele of the insulin receptor gene may be at least partly responsible for some instances of insulin-resistant diabetes. 相似文献
2.
Insulin insensitivity of large fat cells 总被引：6，自引：0，他引：6
Large insulin-insensitive adipocytes from adult rats have normal binding capacities and affinities for insulin. Diminished insulin-like responses to spermine and reduced rates of glucose oxidation are also evident in these cells. The results indicate that the defect responsible for this insulin-resistant state exists in a step subsequent to insulin binding, possibly in transmission of the insulin-receptor "signal" since insensitivity occurs under conditions where glucose transport and oxidative processes are not apparently impaired. 相似文献
3.
A mechanism of extreme growth and reliable signaling in sexually selected ornaments and weapons 总被引：1，自引：0，他引：1
Many male animals wield ornaments or weapons of exaggerated proportions. We propose that increased cellular sensitivity to signaling through the insulin/insulin-like growth factor (IGF) pathway may be responsible for the extreme growth of these structures. We document how rhinoceros beetle horns, a sexually selected weapon, are more sensitive to nutrition and more responsive to perturbation of the insulin/IGF pathway than other body structures. We then illustrate how enhanced sensitivity to insulin/IGF signaling in a growing ornament or weapon would cause heightened condition sensitivity and increased variability in expression among individuals--critical properties of reliable signals of male quality. The possibility that reliable signaling arises as a by-product of the growth mechanism may explain why trait exaggeration has evolved so many different times in the context of sexual selection. 相似文献
4.
Receptor-mediated transport of insulin across endothelial cells 总被引：33，自引：0，他引：33
Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly through the use of dual chambers separated by a horizontal monolayer of cultured bovine aortic endothelial cells. In this setting, endothelial cells took up and released the labeled insulin, thereby transporting it across the cells. The transport of insulin across the endothelial cells was temperature sensitive and was inhibited by unlabeled insulin and by antibody to insulin receptor in proportion to the ability of these substances to inhibit insulin binding to its receptor. More than 80 percent of the transported insulin was intact. These data suggest that insulin is rapidly transported across endothelial cells by a receptor-mediated process. 相似文献
5.
D S Miller 《Science (New York, N.Y.)》1988,240(4851):506-509
Like insulin-sensitive somatic cells, stage IV oocytes from Xenopus laevis increase their synthesis of RNA, protein, and glycogen in response to extracellular insulin. Synthesis of RNA and protein are also increased when oocytes are maintained under paraffin oil and insulin is microinjected into the cytoplasm. The effects of external and intracellular insulin are additive, suggesting separate mechanisms of action. Experiments with nuclei isolated under oil show that RNA synthesis can be stimulated by applying insulin to the nucleus directly. Thus, the nucleus appears to be one intracellular site of hormone action. 相似文献
6.
Proinsulin: metabolic effects in the human forearm 总被引：1，自引：0，他引：1
Five subjects were studied by the forearm perfusion technique with proinsulin at a final plasma conceintration of 1.76 x 10(-9) millimole per milliliter. Two of these subjects were studied with single-component insulin at a concentration of 1.96 x 10(-9) millimole per milliliter. Proinsulin is, in general, biologically less potent than single-component insulin. In contrast to insulin, its effects upon adipose tissue are for the most part greater than upon muscle. 相似文献
7.
After insulin binds 总被引：54，自引：0，他引：54
O M Rosen 《Science (New York, N.Y.)》1987,237(4821):1452-1458
Three recent advances pertinent to the mechanism of insulin action include (i) the discovery that the insulin receptor is an insulin-dependent protein tyrosine kinase, functionally related to certain growth factor receptors and oncogene-encoded proteins, (ii) the molecular cloning of the insulin proreceptor complementary DNA, and (iii) evidence that the protein tyrosine kinase activity of the receptor is essential for insulin action. Efforts are now focusing on the physiological substrates for the receptor kinase. Experience to date suggests that they will be rare proteins whose phosphorylation in intact cells may be transient. The advantages of attempting to dissect the initial biochemical pathway of insulin action include the wealth of information about the metabolic consequences of insulin action and the potential for genetic analysis in Drosophila and in man. 相似文献
8.
Adenosine 3',5'-monophosphate in pancreatic islets: glucose-induced insulin release 总被引：13，自引：0，他引：13
M A Charles R Fanska F G Schmid P H Forsham G M Grodsky 《Science (New York, N.Y.)》1973,179(73):569-571
Glucose-induced release of insulin from perifused rat islets is associated with elevated islet adenosine 3',5'-monophosphate. If values for adenosine 3',5'-monophosphate are compared to insulin release during theophylline or glucose stimulation and theophylline plus glucose stimulation, it suggests a minor role for adenosine 3',5'-monophosphate in directly stimulating insulin release but a prominent role in modulating glucose-induced release of insulin. 相似文献
9.
A diminished response to insulin is exhibited by isolated fat cells obtained from rats that have been either starved, or treated with prednisone, or made diabetic by administration of streptozotocin. This decrease in response is not accompanied by changes in the quantity of insulin receptor of these cells or in the affinity of these receptors for insulin. Similarly, the decreased responsiveness to insulin of fat cells obtained from certain species (hamster, rabbit, mouse, guinea pig) is not explainable in terms of alterations of the insulin receptor. 相似文献
10.
Stanley SA Gagner JE Damanpour S Yoshida M Dordick JS Friedman JM 《Science (New York, N.Y.)》2012,336(6081):604-608
Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells. 相似文献
11.
In the fruit fly Drosophila, four insulin genes are coexpressed in small clusters of cells [insulin-producing cells (IPCs)] in the brain. Here, we show that ablation of these IPCs causes developmental delay, growth retardation, and elevated carbohydrate levels in larval hemolymph. All of the defects were reversed by ectopic expression of a Drosophila insulin transgene. On the basis of these functional data and the observation that IPCs release insulin into the circulatory system, we conclude that brain IPCs are the main systemic supply of insulin during larval growth. We propose that IPCs and pancreatic islet beta cells are functionally analogous and may have evolved from a common ancestral insulin-producing neuron. Interestingly, the phenotype of flies lacking IPCs includes certain features of diabetes mellitus. 相似文献
12.
昆虫滞育是由遗传和环境因子共同作用,导致生长发育停滞的一种重要的生态适应策略;是一个复杂的多基因参与,受多条信号通路调控的独特的发育和生理过程。作为进化上保守的信号通路,胰岛素信号对滞育昆虫的寿命、细胞周期、代谢、能量物质积累和抗逆性等方面具有重要的调控作用。因此,研究胰岛素信号对滞育诱导、滞育维持以及滞育解除的调控作用将有利于揭示昆虫滞育多样化的分子机制,进而为农业害虫的防治提供新的解决思路。本文通过总结胰岛素信号参与昆虫滞育调控的研究进展,为昆虫类胰岛素功能和昆虫滞育的分子调控机制研究提供参考。 相似文献
13.
Insulin biosynthesis: evidence for a precursor 总被引：48，自引：0，他引：48
Human islet cell tumor tissue and isolated islets of Langerhans from rats incorporated radioactive amino acids in vitro into insulin and a larger acid-alcohol soluble protein which could be separated from insulin by gel filtration. The amino acids were incorporated into the larger protein earlier than into insulin; only after incubation of islets for approximately 30 minutes did radioactivity begin to appear in insulin. The transfer of about 70 percent of the radioactivity of the larger protein to insulin was demonstrated in the absence of new peptide bond synthesis (cycloheximide), or during incubation with unlabeled amino acid (chase). The results indicate that the larger protein is a precursor in the biosynthesis of insulin. The name "proinsulin" is suggested for this protein. 相似文献
14.
Cheung AT Dayanandan B Lewis JT Korbutt GS Rajotte RV Bryer-Ash M Boylan MO Wolfe MM Kieffer TJ 《Science (New York, N.Y.)》2000,290(5498):1959-1962
Genetic engineering of non-beta cells to release insulin upon feeding could be a therapeutic modality for patients with diabetes. A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP). Mice expressing this transgene produced human insulin specifically in gut K cells. This insulin protected the mice from developing diabetes and maintained glucose tolerance after destruction of the native insulin-producing beta cells. 相似文献
15.
Yuan M Konstantopoulos N Lee J Hansen L Li ZW Karin M Shoelson SE 《Science (New York, N.Y.)》2001,293(5535):1673-1677
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization. 相似文献
16.
The binding constants and the number of binding sites for insulin, glucagon, epinephrine, cyclic adenosine monophosphate, and calcium ions for the plasma membrane of rat liver were determined by Scatchard plots. The plots are biphasic or multiphasic, an indication of at least two types of binding sites for each ligand. At least three types of binding sites were found for insulin. In the concentration range of 10(-6) to 10(-8) molar, glucagon, epinephrine, and hydro-cortisone increased calcium ion binding to the plasma membrane, whereas insulin decreased this binding. At hormone concentrations of 10(-6) to 10(-7) molar, glucagon was the most effective in increasing calcium binding, but at a hormone concentration of 10(-8) molar, hydrocortisone was the most effective in stimulating calcium binding. Adenosine triphosphate reversed the effect of insulin and inhibited the effect of the other hormones. These studies suggest a relation between hormones and calcium with respect to membrane structure and function. 相似文献
17.
Porcine insulin, which is distinguished from human insulin only in the amino acid at the C terminal of the B chain, is antigenic in man. Even if the last amino acid or the last eight amino acids are removed from the C terminus of the B chain of insulin, the altered insulin still reacts with human antibodies to porcine insulin; thus, the antigenic determinant of porcine insulin is located in a part of the molecule where the amino acid sequence is the same as it is in the corresponding part of the human insulin molecule. 相似文献
18.
Incorporation of phenylalanine into protein by ribosomes from the heart muscle of rats is decreased when the ribosomes are from alloxan-diabetic animals. Protein synthesis is increased when the ribosomes are obtained from nondiabetic animals I hour after treatment with insulin. The change due to insulin appears to be an alteration in the function of the ribosome. 相似文献
19.
Insulin receptors are abundant in the central nervous system, but their roles remain elusive. Here we show that the insulin receptor functions in axon guidance. The Drosophila insulin receptor (DInR) is required for photoreceptor-cell (R-cell) axons to find their way from the retina to the brain during development of the visual system. DInR functions as a guidance receptor for the adapter protein Dock/Nck. This function is independent of Chico, the Drosophila insulin receptor substrate (IRS) homolog. 相似文献
20.
【目的】研究印楝素对min6细胞增殖、葡萄糖摄取及胰岛素分泌的影响,并探讨其作用机制。【方法】不同浓度印楝素处理min6细胞48 h,检测细胞增殖量。在5.5和25.0 mmol·L~(-1)葡萄糖条件下,检测印楝素处理细胞的葡萄糖摄取水平,胰岛素ELISA检测试剂盒检测细胞胰岛素的分泌。【结果】与对照组相比,在5.5和25.0mmol·L~(-1)葡萄糖条件下,印楝素均表现促进细胞增殖活性。印楝素处理下,与25.0 mmol·L~(-1)葡萄糖条件相比,5.5 mmol·L~(-1)葡萄糖表现出更显著地促进葡萄糖摄取和胰岛素分泌的作用。【结论】印楝素可能通过调控葡萄糖水平影响胰岛素的分泌。 相似文献