Immunoreactive definition of TNF- α, HIF-1 α, Kir6.2, Kir3.1 and M2 muscarinic receptor for cardiac and pancreatic tissues in a mouse model for type 1 diabetes

Abstract

AimDiabetes mellitus (DM) is characterized by insulin resistance or hyperglycemia caused by insufficient insulin secretion. Acetylcholine (ACh) can stimulate insulin release depending on glucose while hyperglycemia in DM pathology can cause cellular hypoxia. Adaptive responses to hypoxia in DM are associated with stimulation of hypoxia-inducible factor 1-alpha (HIF-1α) signal due to hyperglycemia. Hypoxia affects potassium (K+) concentration by increasing excitability in K+ ion channels. In our study, we aimed to evaluate the immunoexpression of adaptive responses to hypoxia that develops with DM in pancreatic and cardiac tissues. Materials and methodsIn this study, 14 Balb/C female mice were divided into control and type 1 DM groups. Streptozotocin (STZ; 150 mg/kg/bw) was injected intraperitoneally in mice to create a type 1 diabetes model. During the experiment, diabetic mice with a daily blood-glucose value higher than 250 mg/dl were injected subcutaneously with 1 U/day insulin. Two weeks after STZ injection, the mice were euthanized by cervical dislocation and the heart and pancreatic tissues were removed and prepared for histological and immunohistochemical analysis for TNF-α, HIF-1α, Kir6.2, Kir3.1, and M2 muscarinic receptor. Key findingsSignificant increase of TNF-α, HIF-1α, and Kir6.2 immunoreactivity was observed in both cardiac and pancreatic tissues of type 1 DM mice. And also, cardiac Kir3.1 and M2 muscarinic receptor and pancreatic M2 muscarinic receptor immunoreactivities significantly increased. SignificanceOur study can contribute to understanding the role of Kir3.1, Kir6.2 channels, and hypoxia biomarkers in the type 1 DM mechanism.