A few picks from what I’ve read over the past month:
– binge drinking, or how high alcohol blood levels can disrupt the normal functions of insulin,
– mighty bug, or how a pathogenic bacteria can reprogram host cells,
– celiac disease, or how it may not be all about gluten.
- Insulin resistance and binge drinking
Frequent binge drinking* is linked to an increased risk for developing not only alcohol dependence but also heart disease and type 2 diabetes. A new study published in Science Translational Medicine may help explain the link to type 2 diabetes by identifying a mechanism by which binge alcohol consumption triggers insulin resistance.
Using a model of ethanol (alcohol) exposure in rats, the researchers show that in ethanol-exposed rats glucose tolerance is impaired despite higher insulin blood levels, which suggests that insulin resistance may have developed in these alcohol-treated rats. This effect is observed up to 2 days after the levels of alcohol in the circulation have become undetectable. Investigating the possible causes of insulin resistance, the researchers find that binge-like ethanol exposure decreases the ability of insulin to reduce glucose production by the liver, and that it does so by impairing insulin receptor signaling in the brain, specifically in the hypothalamus. An increased expression of the protein PTP1B, which is a negative regulator of insulin receptor signaling, in the hypothalamus of ethanol-exposed rats may at least in part explain how normal insulin function is affected.
*defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in the US as a blood alcohol level ≥0.8g/L, which corresponds to ≥5 drinks/2 hrs for men, ≥4 drinks/2 hrs for women
(Sci Transl Med 30 January 2013, DOI: 10.1126/scitranslmed.3005123)
- Leprosy bacteria reprogram host cells
Mycobacterium leprae, the bacterium causing leprosy, preferentially infects Schwann cells, which are the cells of the peripheral nervous system that produce the myelin sheath insulating axons (the projections of neurons). As a result, leprosy leads to neurological injury, sensory loss and sensorimotor dysfunction in patients. Although it is known that during late stages of the disease M. leprae spreads to other cell types, such as muscle cells, how the bacterium disseminates has remained elusive.
A study recently published in Cell reveals an unexpected mechanism by which M. leprae may spread. The authors show that Schwann cells infected by M. leprae gradually dedifferentiate, turning off the expression of genes specific to their identity and function. In parallel, the cells turn on embryonic/developmental genes, acquiring stem cell-like properties. The researchers further show that these infected stem-cell like cells may contribute to spreading the bacterium to other cell types either by directly differentiating into muscle cells or by attracting macrophages (immune cells) to which M. leprae is then transferred.
Beyond the relevance to the disease leprosy, this study interestingly shows that a pathogen is capable of exploiting the genomic plasticity of its host cell to reprogram previously differentiated cells and thereby expand the repertoire of cell types it infects.
(Cell 17 January 2013, DOI: 10.1016/j.cell.2012.12.014)
- Non-gluten cereal proteins trigger the innate immune system
In people with celiac disease, the adaptive immune system reacts to gluten proteins present in wheat, barley and rye, leading to atrophy of the intestinal mucosa and nutrient malabsorption. The immune response also turns against the individual’s own molecules, producing autoantibodies that target the enzyme tissue transglutaminase. Although many components of celiac disease are well known (such as the HLA alleles underlying the genetic predisposition or the type of T lymphocytes involved in the adaptive immune response), it has been suspected for some time that the innate arm of the immune system might also be involved in the pathogenesis of the disease.
In a study published in The Journal of Experimental Medicine in December 2012, researchers provide evidence that two non-gluten proteins important for wheat resistance to pests activate the innate immune system. More specifically, the team shows that two molecules dubbed ATIs (for α-amylase-trypsin inhibitors) can engage a receptor complex that usually recognizes pathogen-associated molecules and as a result stimulate the innate immune cells to produce inflammatory mediators.
ATIs are important in cereals for defense against pests and parasites, and it is possible that selective breeding of high-yield and highly pest-resistant wheat has led to an increase in wheat ATI content. The researchers suggest that activation of the innate immune system by ATIs might also play a role in other non-celiac gut inflammatory diseases, e.g. in individuals with gluten sensitivity.
(J Exp Med 3 December 2012, DOI: 10.1084/jem.20102660)