MANIPAL: Scientists at School of Life Sciences, Manipal Academy of Higher Education (MAHE), Manipal, identified key genes influenced by inflammatory mediator, interleukin-6 (IL-6), on endothelial cells associated with insulin resistance.
That could be the reason why Type 2 Diabetic (T2D) patients suffer from vascular diseases despite controlling the glucose levels by insulin or anti-diabetic drugs,” said director, SOLS, K Satyamoorthy who is also the group leader of the team. The extensive research was published in the scientific journal, “Laboratory Investigations”, a Springer-Nature journal.
Satyamoorthy said that the hypothesis behind morbidity associated with vascular diseases in T2D, even after strict control of glucose levels, is due to metabolic memory. “This is based on epigenetic mechanisms and can be regulated by several factors such as inflammation, hyperglycemia, or stress. Hence, studying these epigenetic mechanisms was important and led to the discovery of new genes and mechanisms,” he said.
Normal levels of IL-6 produced by immune cells protect the body from pathogens during infections. However, conditions such as diabetes are associated with sterile inflammation and where there is increased production of IL-6 levels leads to deleterious effects and may even cause insulin resistance.
Manjunath B Joshi, primary scientist added, “It has long been known that the inflammatory molecule IL-6 concentrations are high in serum of T2D patients and we were wondering how IL-6 influences endothelial cells and if there is a role in disturbing insulin function. Our work links high IL-6 levels with decreased insulin function and investigates underlying epigenetic mechanisms”. Ashwath Balakrishnan, the PhD scholar associated with the work at MAHE said, “epigenetic changes caused by key enzyme, DNMT1 is destabilized in response to IL-6 leading to disturbed production of nitric oxide and hence insulin is unable to impart its normal function”.
Dr Vinod Bhat, vice chancellor of MAHE, said, “MAHE is supporting molecular genetics programme as there is plenty to discover to the benefit of patients. Majority of T2D subjects suffer from vascular diseases and it is important to study vascular endothelial cells in order to identify newer therapeutic interventions to restore normal function of the endothelial cells. MAHE is in unique environment that researchers, clinical practitioners and public health experts can work together to bring about change in the society on how the diseases are managed in individuals”.
Dr HS Ballal, pro-chancellor for MAHE said, “We have been striving for societal benefit through our network of hospitals, education institutions with special emphasis on research and developmental activities. The work being carried out at School of Life Sciences is critical to manage chronic diseases such as diabetes and may lead to better clinical practices in future”.