A Mouse Model of Partial Pancreas Agenesis Induced by Polo-like kinase 1 Mutation

The pancreas regulates metabolic homeostasis through exocrine and endocrine pathways. Dysfunction or loss of pancreatic β-cells causes diabetes. Here we explore the role of Polo-like kinase 1 (PLK1) in the pancreas using a pancreatic-lineage specific knockout (Plk1^PKO) mouse model. Plk1^PKO leads to partial pancreatic agenesis, diminishing pancreatic mass. Adult Plk1^PKO mice exhibit diabetic syndromes including hyperglycemia, glucose intolerance, and insulin hypersensitivity. Plk1^PKO mice also exhibit growth retardation and reduced skeletal muscle and adipose tissue masses. Furthermore, Plk1^PKO mice develop metabolic adaptation towards fatty acid utilization, manifested by elevated oxygen consumption (VO₂), reduced respiratory exchange ratio (RER), and more oxidative myofibers. These findings reveal a key role of PLK1 in pancreas development.