Aim: Diabetes 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-1 alpha) 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.