Role of Innate Immunity and Oxidative Stress in the Development of Type 1 Diabetes Mellitus. Peroxiredoxin 6 as a New Anti-Diabetic Agent

Abstract

The review discusses information on the development of type 1 diabetes mellitus (T1D) as a systemic autoimmune and inflammatory disease. Focus of the review is on the role of innate immune system, including activation of some signal ing cascades, cytokine response, and activity of the Toll like receptors in the development of T1D. Dysfunction of innate immunity is the cause of the attack of pancreatic beta cells by the host T lymphocytes, which leads to the death of pancre atic beta cells that produce insulin. Lack of insulin causes hyperglycemia and the need for lifelong injections of insulin in patients with T1D, which, nevertheless, does not exclude damage to many organs and tissues, given particular vulnerabili ty of the blood vessels under conditions of hyperglycemia. The review discusses the role of oxidative stress as a factor that plays a major role in damage of vascular system and pancreatic tissue during the development of T1D. Considering high sen sitivity of pancreatic beta cells to the action of reactive oxygen species (ROS), the possibility of using antioxidants for reduc ing the level of pathological consequences in the course of T1D development is discussed. New information on anti diabetic activity of the exogenous antioxidant enzyme peroxiredoxin 6, which is capable of penetrating cells, activating insulin pro duction in beta cells, reducing ROS levels, as well as decreasing activation of some signaling cascades, production of pro inflammatory cytokines, and expression of Toll like receptors in beta cells and in immune cells during T1D development is discussed.

Pancreas Β-Cells in Type 1 and Type 2 Diabetes: Cell Death, Oxidative Stress and Immune Regulation. Recently Appearing Changes in Diabetes Consequences

“…We have previously demonstrated the protective role of exogenous peroxiredoxin 6 under T1D conditions in a diabetic mouse model and in a rat insulinoma RIN-m5F β-cell model [12][13][14]. In addition, we have recently discussed the role of senescent β-cells in the development of type 1 diabetes, in which we concluded that peroxiredoxin 6 can be qualified as a new protective and senolytic agent in diabetes mellitus [15].…”

The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus

“…Interestingly, the insulin-stimulating activity of Prx6 in vitro was detected both when RIN-m5F β-cells were cultivated under normal conditions and under stressful conditions, inducing cell death [99]. In an alloxan-or streptozotocin-induced mouse model of diabetes, intravenous administration of recombinant Prdx6 prevented hyperglycemia, reduced mortality, restored the plasma cytokine profile, and reduced β-cell destruction in the islets of Langerhans in the mouse pancreas [100][101][102].…”

Pharmacokinetics of Glutapyrone and its Impact on Expression of the Genes Involved in DNA Repair and Free Radical Production in Intact and Diabetic Rats

“…Diabetes mellitus (DM) remains a serious medical and social problem throughout the world. Oxidative stress and impaired DNA repair are important factors in the development of DM and its complications (Ramani et al, 2020;Novoselova et al, 2021;Kopf et al, 2021). DNA repair enzymes are chosen as targets for antidiabetic therapies (Sarras et al, 2014;Abdelali et al, 2016).…”