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Both GLP-1 receptor (GLP-1R) and insulin receptor (IR) transmit signals for insulin release and/or cellular metabolism although using distinct sets of transducing molecules and separate pathways. We proposed a possible association of IR and GLP-1R, since they are coexpressed in diverse tissues including the pancreatic β-cells and crosstalk between their signaling was frequently reported. We showed a specific interaction between GLP-1R and IR which was independent of intracellular receptor domains and not responsive to ligand binding. In signaling, the IRS-1 was coupled more to GLP-1R and less to IR in the receptor complex at IR activation, with subsequent IRS-1 degradation suppressed rather than its activation inhibited. The Gsα recruitment to the activated GLP-1R was inhibited in the GLP-1R/IR complex, with the signaling in cAMP pathway suppressed at IR activation. Therefore, the identified GLP-1R/IR complex recruits their signaling molecules which are differentially modified, leading to a crosstalk between their signaling. • IR and GLP-1R interacts specifically independent of the cellular context. • The complexed GLP-1R/IR recruits their signaling molecules to both receptors. • GLP-1R/IR complexation reduces IR triggered IRS-1 degradation. • IR activation decreases its coupled GLP-1R signaling in Gsα/cAMP pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polygonum capitatum (PC) has both antibacterial and anti-inflammatory effects. • PC has advantages in the treatment of Helicobacter pylori -associated gastritis(HAG). • Network pharmacology lets us quickly predict the action mechanism of PC. • We found that PC affects the phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2. • PC can significantly inhibite the nuclear translocation of NF-κB p65 and p-p38MAPK. Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori -associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment. [ABSTRACT FROM AUTHOR]

Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli . All the tested peptides including glucagon-like peptide 1 (GLP-1), a C -terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting. All recombinant products were expressed in inclusion bodies. The effective accumulation of products was largely attributed to the insoluble expression induced by fusion with insulin chains, and was confirmed by the fusion expression of transthyretin. Insulin chains thus show promise as efficient fusion tags for mass production of heterologous peptides in prokaryotes. [ABSTRACT FROM AUTHOR]