Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

<p>Abstract</p> <p>Background</p> <p>Glycated albumin (GA) is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells.</p> <p>Methods</p> <p>Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA) and GA was measured under three different glucose concentrations, 3 mM (G3), 7 mM (G7), and 15 mM (G15), with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS), and the expression of iNOS-mRNA was investigated by real-time PCR.</p> <p>Results</p> <p>Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (<it>P </it>= 0.920), and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (<it>P </it>= 0.046), for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion.</p> <p>Conclusion</p> <p>GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.</p

Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients

Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder against melanocytes. Polymorphisms of the protein tyrosine phosphatase non-receptor 22 gene (PTPN22) have recently been reported to be associated with susceptibility to several autoimmune diseases. In this study, genetic susceptibility to VKH disease was investigated by screening for single nucleotide polymorphisms (SNPs) of PTPN22. Methods: A total of 167 Japanese patients with VKH disease and 188 healthy Japanese controls were genotyped by direct sequencing methods for six SNPs (rs3811021, rs1217413, rs1237682, rs3761935, rs3789608, and rs2243471) of PTPN22 including the uncoding exons. Results: The six SNPs in PTPN22 showed no significant association with susceptibility to VKH disease or its ocular, neurologic, or dermatological manifestation. Conclusions: Further studies are needed to clarify the genetic mechanisms underlying VKH disease

Observing and modeling the sequential pairwise reactions that drive solid-state ceramic synthesis

Solid-state synthesis from powder precursors is the primary processing route to advanced multicomponent ceramic materials. Designing ceramic synthesis routes is usually a laborious, trial-and-error process, as heterogeneous mixtures of powder precursors often evolve through a complicated series of reaction intermediates. Here, we show that phase evolution from multiple precursors can be modeled as a sequence of pairwise interfacial reactions, with thermodynamic driving forces that can be efficiently calculated using ab initio methods. Using the synthesis of the classic high-temperature superconductor YBa$_2$Cu$_3$O$_{6+x}$ (YBCO) as a representative system, we rationalize how replacing the common BaCO$_3$ precursor with BaO$_2$ redirects phase evolution through a kinetically-facile pathway. Our model is validated from in situ X-ray diffraction and in situ microscopy observations, which show rapid YBCO formation from BaO$_2$ in only 30 minutes. By combining thermodynamic modeling with in situ characterization, we introduce a new computable framework to interpret and ultimately design synthesis pathways to complex ceramic materials

Transplantation of human iPSC-derived muscle stem cells in the diaphragm of Duchenne muscular dystrophy model mice

マウスの横隔膜にヒトiPS細胞から作った骨格筋幹細胞を移植する --デュシェンヌ型筋ジストロフィーの呼吸筋治療に向けた横隔膜移植方法の確立--. 京都大学プレスリリース. 2022-04-13.Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm