Simplified Protocol for Production of Persistent Hyperglycemic Zebrafish Model for Type II Diabetes Mellitus Studying

Diabetes mellitus (DM) is a metabolic disorder characterized by extremely elevated blood sugar, i.e. hyperglycemia (HG). This hyperglycemia is caused by either defective insulin production, marking DM type 1 (T1DM), or impaired biological effects of insulin by developing insulin resistance, marking DM type 2 (T2DM). Zebrafish Danio rerio provides an excellent model for testing T2DM therapies, having a great resemblance to humans’ metabolic pathways related to T2DM development. In the current study, two different glucose immersion protocols were tested to induce persistent HG in zebrafish Danio rerio. The first included prolonged immersion of the fish in gradually elevating glucose concentrations, i.e. 45, 90, and 200mM glucose monohydrate. The second was through prolonged immersion of fish in a fixed concentration of glucose, i.e., 90mM. Both were followed by a recovery period of fish in glucose-free waters. Glucose and triglycerides were assessed in the livers of immersed fish after i) full-time immersion in glucose, and ii) the recovery period in glucose-free waters. Only the “fixed-dose” immersion protocol resulted in significant HG and hypertriglyceridemia (HTG) after the glucose immersion. A recovery period in glucose-free waters could make glucose-challenged fish recover neither from HG nor HTG. The results indicated the feasibility of fixed immersion of adult zebrafish in 90mM of glucose solution in the induction of persistent HG and HTG, rather than the “gradually elevating” glucose immersion protocol. The identified induction protocol can be recommended for testing different therapies aiming to combat T2DM by affecting both HG and HTG.