ISOLATION/CHARACTERIZATION OF SULFONYLUREA-LIKE COMPOUNDS AND INSULIN RELEASE

磺酰脲类化合物的分离/表征和胰岛素释放

• 批准号: 6288650
• 负责人: Robert L Eskay
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288650
• 关键词: drug receptors; endocrine pharmacology; glucose metabolism; pancreatic islet function; peptides; pituitary gland; receptor binding; sulfonylurea

Selected serotonergic compounds, through a CNS-site of action, appear to be able to release sulfonylurea-like peptides from the pituitary gland. The therapeutic significance of sulfonylurea compounds, like glibenclamide and tolbutamide, in the treatment of type II diabetes for regulating plasma glucose levels has been recognized for decades without a full appreciation of the mechanism of action of these compounds, nature of the receptor, or the demonstration of the existence of endogenous ligands. After extensive isolation and characterization of sulfonylurea-like activity in the CNS and pituitary gland, several peptide fractions have emerged from the pituitary gland which: (1) enhance insulin secretion, (2) inhibit sulfonylurea drug binding to sulfonylurea receptors, and (3) appear to mimic the electrophysiological membrane changes observed with sulfonylurea drugs. A novel peptide and a known peptide with a novel function have emerged from these studies. It is envisioned that there exists a family of novel endogenous peptides which modulate sulfonylurea receptors.We have demonstrated that a member of the non-histone nuclear protein group mimics many of the actions of the sulfonylurea compounds and this compound appears to be an intracellular regulator of the sulfonylurea receptor. Only data analysis and manuscript work were performed on this project. - behavioral/mental health research, toxicology, neurosciences, endocrine system, CNS, methodological studies

选定的血清素能化合物通过中枢神经系统作用，似乎能够从垂体中释放出磺酰尿素样的肽。数十年来确认了磺酰脲化合物（如Glibenclamide和tolbutamide）在II型糖尿病治疗用于调节血浆葡萄糖水平的II型糖尿病中的治疗意义，而没有完全欣赏这些化合物的作用机制，即受体的性质，或者表现出了内源性ligands的作用。在CNS和垂体中磺酰尿素样活性的广泛分离和表征之后，垂体中出现了几种肽级分，这些肽级别从垂体中出现：（1）增强胰岛素的分泌，（2）抑制磺酰尿素药物与硫酸盐受体的结合和（3）与硫酸含量相结合的硫酸含量变化。这些研究已经出现了一种新型肽和具有新功能的已知肽。可以预见的是，存在一个新型内源性肽，它们调节了磺酰脲受体。我们已经证明，非内酮核蛋白质群的成员模仿了磺酰脲化合物的许多作用，而该化合物似乎是硫酸氟化物受体的细胞内调节剂。该项目仅进行数据分析和手稿工作。 - 行为/心理健康研究，毒理学，神经科学，内分泌系统，CNS，方法论研究