Diabetes and Peripheral Artery Disease


An article published in Experimental Biology and Medicine (Volume 245, Issue 9, May, 2020) (https://journals.sagepub.com/doi/pdf/10.1177/1535370220920832) describes a new link between type 1 diabetes and peripheral artery disease. The study, led by Dr. Ayotunde Dokun in the Division of Endocrinology and Metabolism at the University of Iowa in Iowa City, IA (USA), reports that prolonged high glucose levels block signaling pathways which promote blood vessel recovery.

Peripheral arterial disease (PAD) affects millions of people around the world. PAD is characterized by impaired blood flow in blood vessels outside the heart. Critical limb ischemia is a severe form of PAD that is associated with high risk of limb amputation and death. Diabetes significantly increases the likelihood of developing critical limb ischemia in individuals with PAD. It is well known that diabetes constitutes a chronic inflammatory state. However, the contribution of high glucose-induced inflammation to poor PAD outcomes has not been determined.

In the current study, Dr. Dokun and colleagues investigated the role of inflammatory signaling pathways in PAD using endothelial cell and diabetic mouse models. Endothelial cells chronically exposed to high glucose were less sensitive to ischemic activation of the inflammatory pathways essential for vessel recovery. Ruboxistaurin, a drug clinically effective in treating diabetic retinopathy, restored induction of critical inflammatory signaling pathways in endothelial cells exposed to chronic high glucose. Ruboxistaurin also activated inflammatory signaling pathways and restored blood flow in the hind limbs of diabetic mice. These findings suggest that hyperglycemia in diabetes impedes PAD recovery by blocking beneficial inflammatory responses in endothelial cells. Dr. Dokun said: “Hyperglycemia results in chronic inflammation in diabetes with desensitization of the NF-kappa B inflammatory signaling pathway. NF-kappa B desensitization likely occurs in other diseases characterized by chronic inflammation. Restoring sensitivity to NF-kappa B signaling holds promise as therapy for conditions where chronic inflammation contributes to poor outcomes.”

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology & Medicine, said “Dokun and colleagues have performed elegant studies providing a mechanistic explanation of how diabetes-induced inflammation contributes to poor outcomes in peripheral artery disease. This study also provides insight into potential therapies based on modulation of the canonical NF-kappa B signaling pathway.”

Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership, visit www.sebm.org. For anyone interested in publishing in the journal, please visit http://ebm.sagepub.com.

Source: Experimental Biology and Medicine


Categories: Medical Research

Tags: coronavirus, covid, covid-19, SARS-CoV-2, sebm, treatment

About Experimental Biology and Medicine

Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903.

Danna B. Zimmer
Assistant to the Editor-in-Cheif, Experimental Biology and Medicine