Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

Stress exposure alters brain mRNA expression of the genes involved in insulin signalling, an effect modified by a high fat/high fructose diet and cinnamon supplement

In occidental societies, high fat and high sugar diets often coincide with episodes of stress. The association is likely to modify brain energy control. Brain insulin signalling is rarely studied in stressed individuals consuming high fat diets. Furthermore the effects of cinnamon supplement are not known in these conditions. Therefore, we exposed rats, over a 12-week period, to a control (C) or a high fat/high fructose (HF/HFr) diet that induces peripheral insulin resistance. A cinnamon supplement (C+CN and HF/HFr +CN) was added or not. After diet exposure, one group of rats was exposed to a 30-min restraint followed by a 10-min open-field test, their combination featuring a moderate stressor, the other rats staying unstressed in their home cages. The insulin signalling in hippocampus and frontal cortex was studied through the mRNA expression of the following genes: insulin receptor (Ir), insulin receptor substrate (Irs1), glucose transporters (Glut1 and Glut3), glycogen synthase (Gys1) and their modulators, Akt1 and Pten. In C rats, stress enhanced the expression of Ir, Irs1, Glut1, Gys1 and Akt1 mRNA. In C+CN rats, stress induced an increase in Pten but a decrease in Gys1 mRNA expression. In HF/HFr rats, stress was associated with an increase in Pten mRNA expression. In HF/HFr+CN rats, stress increased Pten mRNA expression but also decreased Gys1 mRNA expression. This suggests that a single moderate stress favours energy refilling mechanisms, an effect blunted by a previous HF/HFr diet and cinnamon supplement

A new classification of earthquake-induced landslide event sizes based on seismotectonic, topographic, climatic and geologic factors

Background This paper reviews the classical and some particular factors contributing to earthquake-triggered landslide activity. This analysis should help predict more accurately landslide event sizes, both in terms of potential numbers and affected area. It also highlights that some occurrences, especially those very far from the hypocentre/activated fault, cannot be predicted by state-of-the-art methods. Particular attention will be paid to the effects of deep focal earthquakes in Central Asia and to other extremely distant landslide activations in other regions of the world (e.g. Saguenay earthquake 1988, Canada). Results The classification of seismically induced landslides and the related ‘event sizes’ is based on five main factors: ‘Intensity’, ‘Fault factor’, ‘Topographic energy’, ‘Climatic background conditions’, ‘Lithological factor’. Most of these data were extracted from papers, but topographic inputs were checked by analyzing the affected region in Google Earth. The combination and relative weight of the factors was tested through comparison with well documented events and complemented by our studies of earthquake-triggered landslides in Central Asia. The highest relative weight (6) was attributed to the ‘Fault factor’; the other factors all received a smaller relative weight (2–4). The high weight of the ‘Fault factor’ (based on the location in/outside the mountain range, the fault type and length) is strongly constrained by the importance of the Wenchuan earthquake that, for example, triggered far more landslides in 2008 than the Nepal earthquake in 2015: the main difference is that the fault activated by the Wenchuan earthquake created an extensive surface rupture within the Longmenshan Range marked by a very high topographic energy while the one activated by the Nepal earthquake ruptured the surface in the frontal part of the Himalayas where the slopes are less steep and high. Finally, the calibrated factor combination was applied to almost 100 other earthquake events for which some landslide information was available. This comparison revealed the ability of the classification to provide a reasonable estimate of the number of triggered landslides and of the size of the affected area. According to this prediction, the most severe earthquake-triggered landslide event of the last one hundred years would actually be the Wenchuan earthquake in 2008 followed by the 1950 Assam earthquake in India – considering that the dominating role of the Wenchuan earthquake data (including the availability of a complete landslide inventory) for the weighting of the factors strongly influences and may even bias this result. The strongest landslide impacts on human life in recent history were caused by the Haiyuan-Gansu earthquake in 1920 – ranked as third most severe event according to our classification: its size is due to a combination of high shaking intensity, an important ‘Fault factor’ and the extreme susceptibility of the regional loess cover to slope failure, while the surface morphology of the affected area is much smoother than the one affected by the Wenchuan 2008 or the Nepal 2015 earthquakes. Conclusions The main goal of the classification of earthquake-triggered landslide events is to help improve total seismic hazard assessment over short and longer terms. Considering the general performance of the classification-prediction, it can be seen that the prediction either fits or overestimates the known/observed number of triggered landslides for a series of earthquakes, while it often underestimates the size of the affected area. For several events (especially the older ones), the overestimation of the number of landslides can be partly explained by the incompleteness of the published catalogues. The underestimation of the extension of the area, however, is real – as some particularities cannot be taken into account by such a general approach: notably, we used the same seismic intensity attenuation for all events, while attenuation laws are dependent on regional tectonic and geological conditions. In this regard, it is likely that the far-distant triggering of landslides, e.g., by the 1988 Saguenay earthquake (and the related extreme extension of affected area) is due to a very low attenuation of seismic energy within the North American plate. Far-distant triggering of landslides in Central Asia can be explained by the susceptibility of slopes covered by thick soft soils to failure under the effect of low-frequency shaking induced by distant earthquakes, especially by the deep focal earthquakes in the Pamir – Hindukush seismic region. Such deep focal and high magnitude (> > 7) earthquakes are also found in Europe, first of all in the Vrancea region (Romania). For this area as well as for the South Tien Shan we computed possible landslide event sizes related to some future earthquake scenarios