高胰岛素血症细胞模型 z-bio 2021-10-14 341

　　CRISPR/Cas9 pancreatic β-cell differentiation-mediated congenital hyperinsulinemia-related clinical symptoms model congenital hyperinsulinemia and ABCC8-deficient human embryonic stem cells. Congenital hyperinsulinemia is a syndrome of hyperinsulinemia and hypoglycemia caused by the secretion of high insulin by pancreatic beta cells caused by gene mutations. The incidence is 1/2500-1/50000. The main molecular pathology basis is the ABCC8 mutation in KCNJ11 and KCNJ11 genes. Each leads to abnormal functions encoded by the KATP channel proteins SUR1 and Kir6.2 subunits. There have been reports on mouse simulation studies of congenital hyperinsulinemia, but pathological models of humanized in vitro cell lines are still lacking.

　　This research uses CRISPR/Cas9 technology to establish a mutant cell line with inactivated ABCC8 gene based on the embryonic stem cell line H1-. Compared with the wild-type cell line, the islet β-like cells induced by the ABCC8 mutant cell line are more effective in secreting insulin and C-peptide, and can better reproduce the clinical manifestations of congenital hyperinsulinemia in vitro. The response of ABCC8 mutant pancreatic β-like cells to a variety of drugs that promote or transplant insulin secretion provides the basis for an in vitro high-throughput drug screening model.

　　Liu Haikun of the Li Yinxiong research team and his colleagues published an article in the journal Plos One, which involved improving the efficiency and mechanism of direct differentiation of human ips cells into pancreatic β cells. Testosterone can increase the efficiency of human induced pluripotent stem cells to produce insulin. In cooperation with Guangzhou Fidelity Hospital, the research team collected male patients with multiple endocrine tumor syndromes, in which pancreatic cancer is related to the clinical phenotypes of high androgen, high insulin and low blood sugar. This also has very similar clinical symptoms. The two genetic diseases with hyperandrogen/hyperinsulinemia/hypoglycemia coupling are polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH). Inspired by these clinical phenomena, to deal with the problem of inefficient differentiation of pancreatic β-cells. Among many stem cells in the industry, subjects have tripled the efficiency of androgen β-cell differentiation. I found that I could do it and explained it. The mechanism behind. This research not only optimizes the existing procedures in methodology, but more importantly, provides medical help to explain some basic genetic diseases, especially the syndrome of type II diabetes, for clinical use of androgens to improve islets β cell function.