Simulated Cholinergic Reinnervation of β (INS-1) Cells: Antidiabetic Utility of Heterotypic Pseudoislets Containing β Cell and Cholinergic Cell

Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase (p<0.0001) in insulin secretion from the coculture group, while in the 3D culture condition, a 1.78-fold increase (p<0.0001) in insulin secretion from heterotypic pseudoislet group was observed. Glucose-stimulated insulin secretion (GSIS) from 2D INS-1 cells showed minimal changes when compared to 3D structures. E-cadherin expressed in INS-1 and NG108-15 cells was the key adhesion molecule for the formation of heterotypic pseudoislets. NG108-15 cells hardly affected the proliferation of INS-1 cells in vitro. Heterotypic pseudoislet transplantation recipient mice reverted to normoglycemic levels faster and had a greater blood glucose clearance compared to INS-1 pseudoislet recipient mice. In conclusion, cholinergic cells can promote insulin-secreting cells to function better in vitro and in vivo and E-cadherin plays an important role in the formation of heterotypic pseudoislets

Resveratrol Attenuates hIAPP Amyloid Formation and Restores the Insulin Secretion Ability in hIAPP-INS1 Cell Line via Enhancing Autophagy

It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors that can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP. Our research demonstrates that amyloid deposition existed in hIAPP-INS1 cell by the thioflavin S fluorescent staining, meanwhile the function of insulin secretion of hIAPP-INS1 cells was decreased significantly (p < 0.01). After treatment with resveratrol (20 μM) for 24 h, amyloid deposition in hIAPP-INS1 cells was decreased significantly, and the insulin secretion was restored significantly (p < 0.01). Once inhibited the autophagy of hIAPP-INS1 cells by 3-methyladenine for 24 h, resveratrol does not effectively remove hIAPP deposits again, and cannot improve the function of insulin secretion. These results provide a novel thought that resveratrol can degrade the amyloid deposition in type 2 diabetes and the graft after islet transplantation.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Evolution of Non-Metallic Inclusions in 27SiMn Steel

To study the evolution of non-metallic inclusions in 27SiMn steel, the 27SiMn steel produced using the LD-LF-CCM process was sampled in various stages in a steel factory. The evolutionary behavior of inclusion in various processes was systematically analyzed by scanning electron microscopy (SEM-EDS), and the total oxygen content and nitrogen content in 27SiMn steel were measured at various production steps. On the basis of the calcium treatment for 27SiMn steel, the equilibrium reactions for Ca-Al were calculated according to the thermodynamic equilibrium model. The results showed that the types of inclusions at the start of LF stations are mainly Al2O3-FeO and MnS-Al2O3. Before calcium treatment, the inclusions are mostly calcium aluminate and CaO-MgO-Al2O3. Compared with the process after soft blowing, the number density of inclusions in tundish increased by 77.88%, possibly due to secondary oxidation. From the soft blowing process to the continuous casting round billet, the inclusions translate into spherical CaO-MgO-Al2O3-SiO2, and a large number of CaS were observed. One part of the CaS precipitated separately, the other part was semi-wrapped with the composite inclusions. At the same time, calcium treatment increases the number density, mean diameter, and the area fraction of inclusions. The mass fraction of T.O. (total oxygen content) increased significantly after soft blowing, and the N content increased greatly from station to tundish. The change trend of N content in steel was basically consistent with that of T.O. content. It was necessary to prevent the secondary oxidation of molten steel during calcium treatment and the casting process. When the liquidus temperature of liquid steel is 1873 K, w[Al] = 0.022%, and w[Ca] in steel is controlled between 1.085 × 10−6 and 4.986 × 10−6, the Al2O3 inclusion degeneration effect is good