Tag: Dr. Norris

Sirtuin1 is a protein that is essential for health. Insulin resistance results when sirtuin1 is lost from skeletal muscle. A team at the University of Iowa led by Drs. Kaiko Irani and Qiuxia Li investigated the impact of sirtuin1 in the vasculature. To accomplish this they knocked out sirtuin1 from the cells that line the inside of blood vessels. As expected, the resulting blood vessels were dysfunctional. Typically, skeletal muscle will become insulin resistant when blood vessels are dysfunctional . However, in this case, the skeletal muscles of the mice lacking blood vessel sirtuin1 were unexpectedly more sensitive to insulin. Importantly, to understand this surprising finding the investigative team identified the mechanism that increases muscle insulin sensitivity. Specifically, the loss of sirtuin1 caused the blood vessel cells to secrete thymosin beta-4, an enhancer of insulin sensitivity in skeletal muscle. These findings highlight the complex actions of sirtuin1 on insulin sensitivity. The publication resulting from the work is entitled “Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome”, is published in the journal Nature Communications, and can be found at this link. Dr. Norris from our division is a co-author on the manuscript and contributed to the work by helping direct the studies measuring muscle insulin sensitivity.

Since 2017, the F.O.E. Diabetes Research Center has maintained a NIH supported Diabetes Research Training Program for postdoctoral scholars. The purpose of this Program is mentor and train the next generation of investigators who will devise better approaches to prevent, treat, and ultimately reverse diabetes. The Training Program is led by Dr. Norris from our Division. The Program supports up to 6 concurrent postdoctoral trainees. This spring, the Program had an unprecedented number of outstanding applicants. To better support training under these circumstances, Dr. Norris partnered with Dr. Bertha Martín, one of the applicants, and her mentor Dr. Jon Resch to create a grant supplement application. This application has now been funded, as NIH grant 3T32DK112751-07S1. We look forward to Dr. Martín’s research development.

Persons with cystic fibrosis typically have an imbalance in their fatty acid levels. A prominent aspect of this imbalance is a deficiency of linoleic acid, which is one of the so-called essential fatty acids. Despite decades of research, the mechanisms of the imbalance are not fully understood. To better understand this fatty acid imbalance, a group of researchers at the University of Iowa, Kansas State University, and the Karolinska Institutet in Stockholm Sweden worked together to study pigs and ferret with cystic fibrosis. The results showed that the imbalance exists at birth even before first feeding. This result argues strongly against one of the leading prior hypotheses which was that the imbalance might stem from the nutrient malabsorption that occurs in cystic fibrosis. Instead, the results suggest that several molecular mechanisms might be responsible for the imbalance, including excess metabolism of arachidonic acid, oxidative isomerization of unsaturated fatty acids, and/or biliary loss of phospholipids containing unsaturated fatty acids. The senior author of the resulting manuscript describing the findings was Dr. Norris from our Division. The work can be found published in the journal Clinical Science (link).

For reasons that are not well understood, persons with cystic fibrosis are at very high risk to develop diabetes. A major factor in this risk is poor secretion of insulin from beta-cells. A research team at the University of Iowa has now published findings that may have identified one of the root causes. The team found exceptionally high levels of reactive oxygen species in pancreas with cystic fibrosis. Furthermore, the islets isolated from cystic fibrosis pancreases exhibited increased production of reactive oxygen species and impaired secretion of insulin. However, two different approaches aimed at reducing or neutralizing excess reactive oxygen species production failed to improve insulin secretion. Nonetheless, the findings highlight what might be an important contributor to poor insulin secretion in persons with cystic fibrosis. From our division, Dr. Andrew Norris contributed to the research and publication. The paper can be found at this DOI link and a full text version can be found at this PubMed Central link.