来源：基因编辑技术

基因编辑又有新进展！通过使用CRISPR/Cas9这一基因魔剪，研究人员成功将一个对调节糖尿病相关的TXNIP基因发挥重要作用的基因敲除，结果发现可以减少胰岛β细胞死亡，增加胰岛素分泌。研究成果发表在The International Journal of Biochemistry & Cell Biology 上。

在一项最新研究中，研究人员对一组叫做组蛋白乙酰转移酶（HAT）的蛋白功能进行了研究，它在TXNIP基因的调节中发挥关键作用，而TXNIP基因表达在高血糖情况下会导致胰岛β细胞死亡，从而减少胰岛素生成。

研究人员比较了2型糖尿病患者产生胰岛素的胰岛细胞和健康人体产生胰岛素的胰岛细胞，结果发现糖尿病患者胰岛细胞中HAT酶的基因活性比在健康人中高出两倍。之后，研究人员通过基因敲除手段敲除该酶的基因，从而研究了它对糖尿病的作用。事实证明确实有所发现。

研究人员使用CRISPR/Cas9将大鼠胰岛细胞遗传密码中控制HAT酶功能的基因序列进行敲除，结果导致TXNIP基因活性降低，从而减少胰岛细胞的死亡，增加了胰岛素的产生。

“我们的研究表明HAT酶在调节TXNIP基因中起关键作用，而通过靶向这种机制，我们改善了胰岛素分泌并防止细胞死亡。”这项研究的通讯作者Yang De Marinis说道，“CRISPR/Cas9是近年来在分子遗传学中最重要的发现之一，我们非常高兴能够在我们的研究团队中建立这种尖端的技术，它开辟了研究无数与糖尿病相关基因功能的可能性，我们正在努力进一步优化这项技术，使其尽可能更高效、更准确。”

With the help of the CRISPR/Cas9 gene scissors, researchers at Lund University Diabetes Centre in Sweden have managed to "turn off" an enzyme that proved to play a key role in the regulation of the diabetes-associated TXNIP gene. The results are decreased cell death and increased insulin production in the genetically modified pancreatic beta cells.

In a recent study, researchers have conducted an investigation on a group of enzymes, histone acetyltransferases (HATs), which play a crucial role in the regulation of the TXNIP gene that, in cases of high blood sugar levels, leads to beta cell death and reduced insulin production.

The researchers compared donated insulin -producing pancreatic islets from type 2 diabetes patients with those from healthy people and discovered that the gene activity of HAT enzymes is twice higher in diabetic cells than in the healthy ones. Following this discovery, the goal was to remove the genetic function of the enzyme to study its effect on diabetes. And this proved to be successful.

Using CRISPR/Cas9, the researchers were able to remove a sequence in the genetic code that controls the function of the HAT enzyme in insulin-producing cells from rats. This resulted in reduced TXNIP gene activity, and thereby reduced cell death and increased insulin production.

"Our research shows that HAT enzymes play a key role in the regulation of TXNIP gene and that by targeting at this mechanism, we improved insulin secretion and prevent cell death," says researcher Yang De Marinis who led the study. She adds:

"CRISPR/Cas9 is one of the most important discoveries in molecular genetics made in recent years, and we are very happy to have managed to establish this cutting-edge technology in our research team. It opens up new possibilities to study the function of an endless number of genes related to diabetes. We are now working hard to further develop this technology to make it as efficient and accurate as possible."

Yang de Marinis

Associate researcher

Current project

Osteopontin (OPN) is a glycoprotein synthesized and secreted by different cell types from various tissues including bone, kidney, smooth muscle and immune organs. OPN promotes cell survival, migration and adhesion by binding to integrins present on the cell surface. Overexpression of OPN has been associated with several physiological and pathological conditions in response to inflammation and other immunologic disorders. Previous studies have revealed that OPN is up-regulated in the serum of type 1 diabetic patients, in diabetic vascular walls and kidneys. The aim of our investigation is to get a better understanding on the protective effect of OPN in islets, as well as the regulation of OPN expression in normal and diabetic islets in association with different regulatory hormones, e.g. GIP and GLP-1.