In a recent article in the journal Nature Communications, Qiuxia Li, PhD, Research Assistant Professor in Cardiovascular Medicine and member of the Irani Lab, provides fresh perspective on how blood vessels communicate with insulin-sensitive tissues, such as skeletal muscle, and points to new avenues for exploration in treating diabetes.
The article, “Deficiency of endothelial Sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome,” reveals that Sirtuin1—a longevity gene that stimulates insulin’s actions in muscle cells and whose decline in blood vessels is associated with vascular diseases such as atherosclerosis, when absent in the endothelial lining of blood vessels—paradoxically promotes metabolic health by stimulating glucose uptake in skeletal muscle of mice. This phenomenon improves glucose control in these mice. Further, Li and her team showed that this effect is achieved because deficiency of Sirtuin1 leads to upregulation of inflammatory signals in the endothelium.
This research, Li explained, illustrates how the same gene, acting in different types of cells and tissues, can have diametrically opposite effects. “While our team recognizes that more research is needed to fully understand how endothelial Sirtuin1 functions in diabetes and other metabolic diseases, this study offers new insights into its role in metabolic health, and may help in more intelligent design of pharmaceuticals that target Sirtuin1 to treat patients living with diabetes,” she said.
In 2020, Li received a Career Development Award from the American Heart Association (AHA) to examine how the Sirtuin1 in endothelium affects peripheral insulin-sensitive issues, which built upon previous work she did while on the Hematology T32 postdoctoral grant (PI: Steven Lentz, MD, PhD). The research was also made possible by collaborators in the University of Iowa’s Department of Pediatrics, Department of Physiology and Biophysics, the Fraternal Order of Eagles Diabetes Research Center, and the Pappajohn Biomedical Institute at the University of Iowa; the Division of Endocrinology, Diabetes and Hypertension, Department of Medicine at the David Geffen School of Medicine at UCLA; and Boston University School of Medicine. In addition to the AHA, this research was supported by the NIH’s NHLBI and NIDDK, the VA ORD, the Office of Naval Research, the Marfan Foundation, and the Iowa Aging Initiative.