Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

New Develoopment of the Basic Theory of Extenics

In this paper,the new development of three basic theories of Extenics,incluing basic-element theory,extension set theory and extension logic theory ,has been introduced.And the new theoretical frame of Extenics has also been set forth.     

The Optimal Solution of the Model with Physical and Human Capital Adjustment Costs

We prove that the model with physical and human capital adjustment costs has optimal solution when the production function is increasing return and the structure of vetor fields of the model changes substantially when the prodution function from decreasing return turns to increasing return. And it is shown that the economy is improved when the coefficients of adjustment costs become small.     

Die Wirkung des Toluidinblaus und der Thrombokinase auf den Vorgang der Thrombininaktivierung

Summary The disappearance of thrombin—formed in the blood, or added to serum-follows a manomolecular reaction-type. Heparin increases the reaction-velocity of this thrombin-inactivating process.Our investigation established that toluidine blue or kinase, which, according to the literature, bind heparin, strongly reduce the speed of thrombin-inactivation too. Therefore the heparin-binding capacity of these substances is also manifested in the decrease of thrombin-inactivation.     

小麦群体连续选择效应的综合分析

本试验对由信谷核不育基因构成的异效群体内４个性状进行连续两轮歧化选择，并将所得数据进行群体综合分析。结果表明：整个群体的平均表现和变异程度未发明显变化；但群体分布状况有一定改变，尤其是每穗粒数的分布数化较为明显；株高和千粒重的有效因子数估计基本符合小麦遗传实际表现，每穗粒数的有效有效因子数估计略低，说明此性状遗传背景较为简单。     

金刚石薄膜的制备及其性能研究概述

金刚石薄膜是工业界继高温超导材料之后的又一研究热点，近年来的研究工作已经取得了重大进展。文章对国内外学者在金刚石薄膜的制备、特性、生长机理以及摩擦特性等方面的研究进行了综合论述，以推动国内外金刚石薄膜基础研究和应用的发展，并提出要重视金刚石薄膜在摩擦学领域中的应用研究，使之为人类社会带来巨大的经济效益。     

原子结构中的物理理论

本文较系统地介绍了有关原子结构方面的一些基础理论,由定性到定量,并应用量子力学知识描绘了原子结构状态。     

Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.