T2DM: Why Epigenetics?

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder influenced by interactions between genetic and environmental factors. Epigenetics conveys specific environmental influences into phenotypic traits through a variety of mechanisms that are often installed in early life, then persist in differentiated tissues with the power to modulate the expression of many genes, although undergoing time-dependent alterations. There is still no evidence that epigenetics contributes significantly to the causes or transmission of T2DM from one generation to another, thus, to the current environment-driven epidemics, but it has become so likely, as pointed out in this paper, that one can expect an efflorescence of epigenetic knowledge about T2DM in times to come

Causes of early-onset type 1 diabetes: toward data-driven environmental approaches

A new study reveals distinctive metabolic changes that precede the development of type 1 diabetes (T1D), tossing a stone into the quiet waters of T1D immunology and genetics. The causes of these metabolic changes and their relationship to autoimmunity and β cell destruction are not yet known, but the identification of a metabolic phenotype linked to susceptibility to type I diabetes may help pave the way to a new era of investigation of T1D causality

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

First available in BioRxiv doi: http://dx.doi.org/10.1101/063438International audienceBackground. The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.Methods. Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.Results. We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.Conclusions. The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.Trial registration. Clinical-Trial.gov NCT02212522. Registered August 6, 2014.

Allele Dependent DNA Methylation of the Human Insulin Gene Promoter in T2D patients and Controls

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Species-Specific Interactions of Src Family Tyrosine Kinases Regulate Chlamydia Intracellular Growth and Trafficking

Src family kinases (SFKs) regulate key cellular processes and are emerging as important targets for intracellular pathogens. In this commentary, we briefly review the role of SFKs in bacterial pathogenesis and highlight new work on the role of SFKs during the intracellular cycle of Chlamydia species

Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells

Shigella, the causative agent of bacillary dysentery, invades epithelial cells in a process involving Src tyrosine kinase signaling. Cortactin, a ubiquitous actin-binding protein present in structures of dynamic actin assembly, is the major protein tyrosine phosphorylated during Shigella invasion. Here, we report that RNA interference silencing of cortactin expression, as does Src inhibition in cells expressing kinase-inactive Src, interferes with actin polymerization required for the formation of cellular extensions engulfing the bacteria. Shigella invasion induced the recruitment of cortactin at plasma membranes in a tyrosine phosphorylation–dependent manner. Overexpression of wild-type forms of cortactin or the adaptor protein Crk favored Shigella uptake, and Arp2/3 binding–deficient cortactin derivatives or an Src homology 2 domain Crk mutant interfered with bacterial-induced actin foci formation. Crk was shown to directly interact with tyrosine-phosphorylated cortactin and to condition cortactin-dependent actin polymerization required for Shigella uptake. These results point at a major role for a Crk–cortactin complex in actin polymerization downstream of tyrosine kinase signaling

Stem cell transplantation for type 1 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>The use of stem cells to treat type 1 diabetes mellitus has been proposed for many years, both to downregulate the immune system and to provide β cell regeneration.</p> <p>Conclusion</p> <p>High dose immunosuppression followed by autologous hematopoietic stem cell transplantation is able to induce complete remission (insulin independence) in most patients with early onset type 1 diabetes mellitus.</p