Glucagon signalling in the dorsal vagal complex is sufficient and necessary for high‐protein feeding to regulate glucose homeostasis in vivo

High‐protein feeding acutely lowers postprandial glucose concentration compared to low‐protein feeding, despite a dichotomous rise of circulating glucagon levels. The physiological role of this glucagon rise has been largely overlooked. We here first report that glucagon signalling in the dorsal vagal complex (DVC) of the brain is sufficient to lower glucose production by activating a Gcgr–PKA–ERK–K_ATP channel signalling cascade in the DVC of rats in vivo. We further demonstrate that direct blockade of DVC Gcgr signalling negates the acute ability of high‐ vs. low‐protein feeding to reduce plasma glucose concentration, indicating that the elevated circulating glucagon during high‐protein feeding acts in the brain to lower plasma glucose levels. These data revise the physiological role of glucagon and argue that brain glucagon signalling contributes to glucose homeostasis during dietary protein intake.     

Phenotypical enrichment strategies for microarray data analysis applied in a type II diabetes study

Combining results from gene microarrays, clinical chemistry, and quantitative tissue histomorphology in an integrated bioinformatics setting enables prioritization of gene families as well as individual genes in a type II diabetes animal study. This new methodology takes advantage of a time-controlled mouse study as the animals progress from a normal phenotype to that of type II diabetes. Profiles from different levels of the biological hierarchy of unpooled entities provide an encompassing, system-wide view of biological changes. Here, phenotypic changes on the tissue-structural and physiological level are used as statistical covariants to enrich the gene expression analysis, suggesting correlative processes between gene expression and phenotype unlocked by multi-sample comparisons. We apply correlative and gene set enrichment procedures and compare the results to differential analysis to identify molecular markers. Evaluation based on ontological classifications proves changes in prioritization of disease-related genes that would have been overlooked by conventional gene expression analyses strategies.     

Role of benzylsuccinate in the induction of the tutE tutFDGH gene complex of T. aromatica strain T1

Expression of the tutE tutFDGH gene cluster of Thauera aromatica strain T1 was examined by Northern and Western analysis in a wild-type strain and chromosomally deleted strains with or without in-frame deletion plasmids. While expression was observed when the wild-type strain was induced with toluene, various chromosomally deleted strains exhibited little or no expression of the tut genes. In contrast, both wild-type and chromosomally deleted strains expressed the tut genes when induced with benzylsuccinate. We conclude that benzylsuccinate is required for the full induction of the tutE tutFDGH gene cluster of T. aromatica strain T1.