Beta Cell Function and the Nutritional State: Dietary Factors that Influence Insulin Secretion.

Approximately 366 million people worldwide have been diagnosed with type-2 diabetes (T2D). Chronic insulin resistance, decreased functional ß-cell mass, and elevated blood glucose are defining characteristics of T2D. Great advances have been made in understanding the pathogenesis of T2D with respect to the effects of dietary macronutrient composition and energy intake on ß-cell physiology and glucose homeostasis. It has been further established that obesity is a leading pathogenic factor for developing insulin resistance. However, insulin resistance may not progress to T2D unless ß-cells are unable to secret an adequate amount of insulin to compensate for decreased insulin sensitivity. Therefore, pancreatic ß-cell dysfunction plays an important role in the development of overt diabetes. This paper reviews recent research findings on the effects of several micronutrients (zinc, vitamin D, iron, vitamin A), leucine, and the phytochemical, genistein on pancreatic ß-cell physiology with emphasis on their effects on insulin secretion, specifically in the context of T2D.

Eep confers lysozyme resistance to enterococcus faecalis via the activation of the extracytoplasmic function sigma factor SigV.

Enterococcus faecalis is a commensal bacterium found in the gastrointestinal tract of most mammals, including humans, and is one of the leading causes of nosocomial infections. One of the hallmarks of E. faecalis pathogenesis is its unusual ability to tolerate high concentrations of lysozyme, which is an important innate immune component of the host. Previous studies have shown that the presence of lysozyme leads to the activation of SigV, an extracytoplasmic function (ECF) sigma factor in E. faecalis, and that the deletion of sigV increases the susceptibility of the bacterium toward lysozyme. Here, we describe the contribution of Eep, a membrane-bound zinc metalloprotease, to the activation of SigV under lysozyme stress by its effects on the stability of the anti-sigma factor RsiV. We demonstrate that the Δeep mutant phenocopies the ΔsigV mutant in lysozyme, heat, ethanol, and acid stress susceptibility. We also show, using an immunoblot analysis, that in an eep deletion mutant, the anti-sigma factor RsiV is only partially degraded after lysozyme exposure, suggesting that RsiV is processed by unknown protease(s) prior to the action of Eep. An additional observation is that the deletion of rsiV, which results in constitutive SigV expression, leads to chaining of cells, suggesting that SigV might be involved in regulating cell wall-modifying enzymes important in cell wall turnover. We also demonstrate that, in the absence of eep or sigV, enterococci bind significantly more lysozyme, providing a plausible explanation for the increased sensitivity of these mutants toward lysozyme.

Chlorhexidine resistance in a Gram-negative bacterium isolated from an aquatic source.

Aeromonas hydrophila is a Gram-negative bacterium of considerable importance in both clinical, especially nosocomial infections, and zoonotic respects, both aquatic and terrestrial infections. In addition to the ability to thrive in a wide range of conditions, A. hydrophila is resistant to numerous antibiotics and antimicrobials. In conjunction with Kansas State University and the Kansas Water Office, water samples from various locations within Kansas were screened for organisms resistant to chlorhexidine. Chlorhexidine is the active agent in many surgical scrubs, prescription mouthwashes, and other bactericidal and bacteriostatic substances. Aeromonas hydrophila capable of growth in therapeutic levels of chlorhexidine was detected in one of the water samples. The isolate was determined not to be harboring a plasmid, lending to a course of inquiry founded on the premise that the source of chlorhexidine resistance resides within the chromosome. Investigation into efflux pumps (EP) is underway with select resistance-nodulation-cell division (RND) pumps, especially the AheABC EP, being exculpated of responsibility for chlorhexidine resistance following testing with a select EP inhibitor. Inquiry into the major facilitator superfamily (MFS) EPs is underway with specific examination of the EmrB/QacA EPs, as chlorhexidine resistance in Staphylococcus aureus carrying the QacA gene has been observed.

High-molecular-weight cocoa procyanidins possess enhanced insulin-enhancing and insulin mimetic activities in human primary skeletal muscle cells compared to smaller procyanidins.

Dysregulation of glucose metabolism is a primary hallmark of metabolic disease (i.e., diabetes, obesity, etc.). Complementary nonpharmaceutical strategies are needed to prevent and/or ameliorate dysregulation of glucose metabolism and prevent progression from normoglycemia to prediabetes and type 2 diabetes across the lifespan. Cocoa compounds, particularly the procyanidins, have shown promise for improving insulin sensitivity and blood glucose homeostasis. However, the molecular mechanisms by which cocoa procyanidins exert these functions remain poorly understood. Furthermore, cocoa procyanidins exhibit size diversity, and evidence suggests that procyanidin bioactivity and size may be related. Here, we show that a procyanidin-rich cocoa extract elicits an antidiabetic effect by stimulating glycogen synthesis and glucose uptake, independent of insulin. Cocoa procyanidins did not appear to act via stimulation of AMPK or CaMKII activities. Additionally, in the presence of insulin, glycogen synthesis and AKT phosphorylation were affected. These mechanisms of action are most pronounced in response to oligomeric and polymeric procyanidins. These results demonstrate (1) specific mechanisms by which cocoa procyanidins improve glucose utilization in skeletal muscle and (2) that larger procyanidins appear to possess enhanced activities. These mechanistic insights suggest specific strategies and biological contexts that may be exploited to maximize the antidiabetic benefits of cocoa procyanidins.

FAMILIAL LARYNGEAL WEB IN THREE GENERATIONS WITH PROBABLE AUTOSOMAL DOMINANT TRANSMISSION.

We report a family with congenital anterior laryngeal web in three males and two females in three successive generations. The maternal grandmother of our proband had a spontaneous occurrence of the web, which subsequently was transmitted in a probable autosomal dominant pattern. A left vocal cord paralysis was documented in two of the affected members.