CRISPR-Cas9 genome editing was used to introduce the missense N437S variant into the mouse Mrpp3 gene to study the causes of insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet β cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis.
The findings revealed that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population.
→ Science Advances -
24 Sep 2021 • Vol 7, Issue 39 •
doi/10.1126/sciadv.abi7514