Rationale and Objectives: Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH. Methods and Results: Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1 ) IH (achieving a nadir of FI O 2 ϭ 5-6% at 60 cycles/h for 9 h), (2 ) intermittent air as a control, (3 ) IH with ANS blockade (hexamethonium), or (4 ) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 Ϯ 2.7 vs. 49.4 Ϯ 1.5 mg/ kg/min, p Ͻ 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the reduction in whole-body insulin sensitivity during IH was not restored by ANS blockade. Conclusion: We conclude that IH can cause acute insulin resistance in otherwise lean, healthy animals, and that the response is associated with decreased glucose utilization of oxidative muscle fibers, but that it occurs independently of activation of the ANS.
Cutting off carbohydrate supply to longan (Dimocarpus longan Lour.) fruit by girdling and defoliation or by detachment induced 100% abscission within a few days. We used these treatments to study the involvement of reactive oxygen species (ROS) in fruit abscission. Girdling plus defoliation decreased sugar concentrations in the fruit and pedicel and depleted starch grains in the chloroplasts in the cells of abscission zone. Prior to the occurrence of intensive fruit abscission, there was a burst in ROS in the pedicel, which peaked at 1 day after treatment (DAT), when H2O2 in the abscission zone was found to be chiefly located along the plasma membrane (PM). H2O2 was found exclusively in the cell walls 2 DAT, almost disappeared 3 DAT, and reappeared in the mitochondria and cell walls 4 DAT. Signs of cell death such as cytoplasm breakdown were apparent from 3 DAT. The burst of ROS coincided with a sharp increase in the activity of PM-bound NADPH oxidase in the pedicel. At the same time, activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and peroxidase (POD) were all increased by the treatment and maintained higher than those in the control. Accompanying the reduction in H2O2 abundance, there was a sharp decrease in PM-bound NADPH oxidase activity after 1 DAT in the treated fruit. H2O2 scavenger dimethylthiourea (DMTU, 1 g L–1) significantly inhibited fruit abscission in detached fruit clusters and suppressed the increase in cellulase activity in the abscission zone. These results suggest that fruit abscission induced by carbohydrate stress is mediated by ROS. Roles of ROS in regulating fruit abscission were discussed in relation to its subcellular distribution.
Barnacles
strongly adhere to immersed solid substrates using a
mixture of cement proteins (CP) that self-assembles into a permanently
bonded layer and binds the barnacles’ shells to foreign surfaces.
MrCP20 from Megabalanus rosa has been
identified as a putative interfacial CP; however, its functional role
remains uncertain. Since the barnacle shell is primarily composed
of calcite, we carry out molecular dynamics simulations to investigate
the molecular interactions between MrCP20 and calcium carbonate (in
free ionic form and as calcite surface). We find that MrCP20 sequesters
free Ca2+ and CO3
2– ions on
its highly charged surface through disorder–order interplay
of the protein and ions. A similar ordering is seen in the protein
conformational landscape upon interactions with the calcite surface.
Structural examinations indicate that the energetically favorable
interactions with calcium carbonate are mediated by charged functional
groups that flank the structured regions of MrCP20 and networks of
water molecules. In vitro biomineralization experiments
and X-ray diffraction indicate that MrCP20 favors the precipitation
of the less stable vaterite polymorph of CaCO3. Our study
suggests that the barnacles exploit the semi-(dis)ordered nature of
acidic MrCP20 to adhere to surfaces like calcite, thereby regulating
nucleation, growth, or morphology of the mineral, while simultaneously
interacting with other biomolecules in cement.
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