Skeletal muscle-released extracellular vesicles: state of the art

All cells export part of their intracellular content into the extracellular space through the release of various types of extracellular vesicles (EVs). They are synthetized either from the budding of the plasma membrane [i.e., microparticles (MPs, 150-300 nm size)] or from the late endosomes in which intraluminal vesicles progressively (ILVs) accumulate during their maturation into multivesicular bodies (MVBs). ILVs are then released into the extracellular space through MVB fusion with the plasma membrane [i.e., exosomes (50-100 nm size)]. In the context of metabolic diseases, recent data have highlighted the role of EVs in inflammation associated with pancreas dysfunction, adipose tissue homeostasis, liver steatosis, inflammation, and skeletal muscle (SkM) insulin resistance (IR). Among these insulin-sensitive tissues, SkM is the largest organ in human and is responsible for whole-body glucose disposal and locomotion. Therefore, understanding the contribution of SkM-EVs in the development of diabetes/obesity/dystrophy/,-related diseases is a hot topic. In this review, we have summarized the role of SkM-EVs in muscle physiology and in the development of metabolic diseases and identify important gaps that have to be filled in order to have more precise information on SkM-EVs biological actions and to understand the functions of the different subpopulations of SkM-EVs on the whole-body homeostasis

Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells

Elevated levels of fasting insulin release and insufficient glucose-stimulated insulin secretion (GSIS) are hallmarks of diabetes. Studies have established cross-talk between integrin signaling and insulin activity, but more details of how integrin-dependent signaling impacts the pathophysiology of diabetes are needed. Here, we dissected integrin-dependent signaling pathways involved in the regulation of insulin secretion in β-cells and studied their link to the still debated autocrine regulation of insulin secretion by insulin/insulin-like growth factor (IGF) 2-AKT signaling. We observed for the first time a cooperation between different AKT isoforms and focal adhesion kinase (FAK)-dependent adhesion signaling, which either controlled GSIS or prevented insulin secretion under fasting conditions. Indeed, β-cells form integrin-containing adhesions, which provide anchorage to the pancreatic extracellular matrix and are the origin of intracellular signaling via FAK and paxillin. Under low-glucose conditions, β-cells adopt a starved adhesion phenotype consisting of actin stress fibers and large peripheral focal adhesion. In contrast, glucose stimulation induces cell spreading, actin remodeling, and point-like adhesions that contain phospho-FAK and phosphopaxillin, located in small protrusions. Rat primary β-cells and mouse insulinomas showed an adhesion remodeling during GSIS resulting from autocrine insulin/IGF2 and AKT1 signaling. However, under starving conditions, the maintenance of stress fibers and the large adhesion phenotype required autocrine IGF2-IGF1 receptor signaling mediated by AKT2 and elevated FAK-kinase activity and ROCK-RhoA levels but low levels of paxillin phosphorylation. This starved adhesion phenotype prevented excessive insulin granule release to maintain low insulin secretion during fasting. Thus, deregulation of the IGF2 and adhesion-mediated signaling may explain dysfunctions observed in diabetes

Probiotic screening and safety evaluation of lactobacillus strains from plants, artisanal goat cheese, human stools, and breast milk

The aim of this study was to select autochthonous strains of Lactobacillus from stools of healthy infants and adults, human milk, artisanal goat cheese, and fruits and vegetables according to their probiotic properties and safety. From 421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to gastric pH and bile salts; they were used to determine their anti-Helicobacter pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity), and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis factor-α-stimulated HT-29 cells) activities as well as their ability to adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results obtained were compared with three commercial probiotic Lactobacillus rhamnosus GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient according to these activities were subsequently identified by sequencing their 16S rRNA gene, their susceptibility to antibiotics was determi