Lund University, Medical Faculty

Decreased cell death and increased insulin production in pancreatic beta cells with genome edit by CRISPR/Cas9

Using 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.

Yang de Marinis

“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, PhD at Lund University Diabetes Centre 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.”

Publication
The International Journal of Biochemistry & Cell Biology
Published online in October 2016: dx.doi.org/10.1016/j.biocel.2016.10.022
 
Contact
Yang De Marinis, PhD, Lund University Diabetes Centre, +46 (0)40 39 12 46, +46 (0)73 543 34 15, e-mail: yang.de_marinis@remove-this-part.med.lu.se


About CRISPR/Cas9
CRISPR/Cas9 refers to a method of genetic engineering that allows researchers to modify specific genetic codes in living cells, and thereby affect the function.

The method was inspired by the way that streptococcal bacteria defend themselves against viruses by cutting the viral DNA to pieces. CRISPR* provides the “name tags” that make sure that the intervention occurs in the right place, and the enzyme Cas9** constitutes the actual “scissors”. By properly designing such “name tags”, researchers can make changes to a DNA sequence with a high level of precision.
  * CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats.
** Cas9: CRISPR associated protein 9.

Last updated: December 1, 2016
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