CILP-2 is a novel secreted protein and associated with insulin resistance

Genetic association studies have implicated that cartilage intermediate layer protein 2 (CILP-2) confers the risk susceptibility for type 2 diabetes (T2DM). However, it is still unknown whether CILP-2 is involved in the regulation of glucose homeostasis and insulin resistance (IR). In the current study, we initially observed that CILP-2 as a secreted protein was detected in both conditioned medium and lysates of cells transfected with an overexpressed vector. We then found that circulating CILP-2 levels had a progressive increase from normal to impaired glucose tolerance (a pre-diabetic status) and then to diabetes, which was correlated positively with waist-to-hip ratio, triglyceride, fasting blood glucose, 2-h blood glucose after glucose overload, HbA1c, fasting insulin, 2-h plasma insulin after glucose overload, and homeostasis model assessment of insulin resistance but negatively with HDL-C. CILP-2 expression was increased in the liver and muscle but decreased in adipose tissues of obese mice or T2DM patients. Furthermore, we demonstrated that CILP-2 circulating levels were affected by OGTT and Exenatide. CILP-2 overexpression resulted in impaired glucose tolerance and hepatic IR in vivo and increased PEPCK expression whereas suppressed phosphorylation of insulin receptor and Akt kinase in vitro. Based on these findings, we have identified a direct interaction between CILP-2 and PEPCK and suggested that CILP-2 plays an important role in the regulation of hepatic glucose production.

Coupling Relationship between Shelf-Edge Trajectories and Slope Morphology and Its Implications for Deep-Water Oil and Gas Exploration: A Case Study from the Passive Continental Margin, East Africa

Both the shelf-edge trajectories and slope morphology are indicative of deep-water sedimentation, but previous studies are relatively independent from each other in the two dimensions. An integrated investigation can enhance the understanding of deep-water sedimentary systems and enrich reservoir prediction methods. Based on the bathymetry data and seismic data published, this study identified ten slope areas at the continental margin of East Africa and classified the clinoforms into three types: concave-up, sigmoidal and planar. Combined with the distribution of main modern rivers in East Africa, nine modern source-to-sink systems were identified and the catchment area is positively correlated with the size of the shelf-edge delta. It is found that the slope morphology of East Africa is closely related to the geological setting, sediment supply and sediment transport pathway in submarine canyon of passive continental margin. When the sediment supply is stable, the concave-up slopes are dominated by the river-associated and shelf-incising canyons and the sigmoidal slopes are determined by the headless canyons. There exists a strong coupling relationship between the shelf-edge trajectories and slope morphology. In general, concave-up slopes correspond to descending trend, flat and low-angle ascending trend shelf-edge trajectories and high-quality reservoirs developed on the basin floor under the influence of river-associated and shelf-incising canyons which have bright prospects for oil and gas exploration. Additionally, sigmoidal slopes usually correspond to descending trend, flat and low-angle ascending trend shelf-edge trajectories at times of relative sea-level fall and the reservoirs mostly developed on the upper slope under the influence of headless canyons. Moreover, the planar slopes correspond to high-angle ascending trend trajectories which are hardly potential for exploration. The coupling model built in this study will provide an insight for oil and gas exploration in deep-water areas with limited data and low exploration degree.