Human INS peptide

Islet inflammation severely impairs pancreatic beta-cell function, but the specific mechanisms are still unclear. Interleukin1-beta (IL-1 beta), an essential inflammatory factor, exerts a vital role in multiple physio-pathologic processes, including diabetes. Calcium/calmodulin-dependent serine protein kinase (CASK) is an important regulator especially in insulin secretion process. This study aims to unveil the function of CASK in IL-1 beta-induced insulin secretion dysfunction and the possible mechanism thereof. Islets of Sprague-Dawley (SD) rats and INS-1 cells stimulated with IL-1 beta were utilized as models of chronic inflammation. Insulin secretion function associated with Cask and DNA methyltransferases (DNMT) expression were assessed. The possible mechanisms of IL-1 beta-induced pancreatic beta-cell dysfunction were also explored. In this study, CASK overexpression effectively improved IL-1 beta-induced islet beta-cells dysfunction, increased insulin secretion. DNA methyltransferases and the level of methylation in the promoter region of Cask were elevated after IL-1 beta administration. Methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC) and si-DNMTs partially up-regulated CASK expression and reversed potassium stimulated insulin secretion (KSIS) and glucose-stimulated insulin secretion (GSIS) function under IL-1 beta treatment in INS-1 and rat islets. These results reveal a previously unknown effect of IL-1 beta on insulin secretion dysfunction and demonstrate a novel pathway for Cask silencing based on activation of DNA methyltransferases via inducible nitric oxide synthase (iNOS) and modification of gene promoter methylation.

The conventional velocity updating algorithms are sufficient for the low and medium-accuracy strapdown INS. However, the accuracy of conventional algorithms is not sufficient for a high-accuracy strapdown INS and the high-dynamic environment. To solve this issue, a new velocity updating algorithm is proposed in this paper. It employs two auxiliary frames to reduce the rate of change in direction of the specific force and angular rate vectors. The first slewing frame slews at a constant rate about a fixed axis in the vehicle frame and the second slewing frame slews at a constant rate about a fixed axis in the first slewing frame. With the proper choice of slew rates, the angular rate and specific force vectors of the second slewing frame changes direction more slowly than that of the vehicle frame. Integrating of the transformed specific force vector in the second slewing frame and then translating it to the navigation frame could determine the updated velocity. The velocity updating algorithm presented in this paper does not involve sculling correction. Simulation and trial results demonstrated that this algorithm has a higher accuracy than the conventional algorithms. This algorithm plays an important role in the high-dynamic environment and a high-accuracy strapdown INS. (C) 2020 Elsevier Masson SAS. All rights reserved.