Summer Research Description: Pancreatic β-cells play a crucial role in glucose homeostasis, secreting insulin to regulate blood glucose levels. When insulin signaling activity is impaired due to obesity or genetic predisposition, more insulin is required to maintain glucose homeostasis. The increased insulin demand initially elicits a compensatory increase of β-cell mass and function but, eventually causes β-cell dysfunction, resulting in type 2 diabetes mellitus (T2DM). T2DM is currently a growing pandemic that has doubled globally in the past three decades. Here we examine the role of the insulin signaling pathway in regulation of β-cell number dynamics in zebrafish. Specifically, we will determine whether zebrafish mutants for insulin a (insa), insulin b (insb), insulin receptor a (insra), and insulin receptor b (insrb) have abnormal glucose metabolism and/or β-cell numbers. Because of the genetic and chemical tractability, these mutant zebrafish may provide a platform for identification of drugs and drug targets for the treatment of insulin resistance and T2DM.