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) mouse model. Plk1 leads to partial pancreatic agenesis, diminishing pancreatic mass. Adult Plk1 mice exhibit diabetic syndromes including hyperglycemia, glucose intolerance, and insulin hypersensitivity. Plk1 mice also exhibit growth retardation and reduced skeletal muscle and adipose tissue masses. Furthermore, Plk1 mice develop metabolic adaptation towards fatty acid utilization, manifested by elevated oxygen consumption (VO), reduced respiratory exchange ratio (RER), and more oxidative myofibers. These findings reveal a key role of PLK1 in pancreas development.