Scientists from the Centre for Cellular & Molecular Biology (CCMB) have found that knocking out a gene in mice led to higher insulin production and better glucose tolerance. The finding holds the potential for drug targeting to treat diabetes.
The team, led by Dr. Satish Kumar, serendipitously found that knocking out the WDR13 gene resulted in hyper insulin secretion and improved glucose clearance. The team genetically engineered a mouse by knocking out the gene, which is conserved in all organisms from fish to humans and encodes a protein. It is a member of the WD-repeat proteins that have a wide range of cellular functions. The increase in insulin production was caused by enhanced beta cell proliferation and higher islet mass in pancreas. This gene was knocked out for the first time, said Vijay Pratap Singh, lead author of the study which was published online in science journal PLoS ONE recently.
The test animals went on to develop mild obesity as they aged. Interestingly, however, they continued to have better glucose clearance in spite of mild obesity. It was not yet known if the obesity was due to higher insulin levels or some different function of the gene.
Dr. Satish Kumar told The Hindu that by inhibiting the functions of this protein, insulin production could be enhanced.
“Indirectly, we discovered a drug target because now we know that if we interfere with this protein, there is more insulin,” he said. However, he noted that there was also a flip side to the finding. While there was no problem with the ‘knockout' mice up to one year, subsequently their cell proliferation increased — such a phenomenon could lead to tumours. The researchers were not aware of WDR13's function of regulating cell division. The real challenge would be to develop a drug which would interfere in a limited way with the functioning of the gene so as to avoid rapid cell proliferation.
Dr. Kumar said their research initially was not related to diabetes. “We were doing basic biology. This is a side implication with an interesting lead.”
CCMB Director Mohan Rao said: “We are trying to decipher the cause for increase in fatty cells and the pancreatic cells.” There is scope for drug development if the two could be separated.