Evaluation of Pancreatic Endocrine Reprogramming in Diabetic Cats

Transcription factors control the development of the endocrine pancreas in various mammals. In humans, paired box-4 (PAX4) and aristaless-related homeobox (ARX) allocate endocrine progenitor cells toward β-cell and α-cell specification, respectively. In adulthood, PAX4 contributes to reprogramming α-cells into β-cells and exocrine into endocrine cells; induction of ARX in β-cells drives them to reprogram into α-cells. Feline diabetes mellitus has a similar pathophysiology to human type 2 diabetes, but information about the role of these transcription factors is unavailable in diabetic cats. The study aim was to test whether diabetic cats have an increased number of pancreatic cells expressing developmental markers of β- and α-cells, respectively, suggesting reprogramming. In 9 diabetic and 9 well-matched control cats, pancreas was collected, formalin-fixed and paraffin-embedded. Tissue slides were labelled for insulin, glucagon, PAX4, and ARX. Positive cells for each marker and double-positive cells for their combinations were counted in the pancreas and compared between groups. Against controls, diabetic cats had fewer insulin-positive cells in the islets (p = 0.001) and exocrine pancreas (p = 0.038); glucagon-positive cells were similar. In the islets, diabetic cats had higher counts of insulin/glucagon-positive cells (p = 0.024), PAX4-positive cells (p = 0.038), as well as PAX4/insulin-positive cells (p = 0.027). In conclusion, in diabetic cats, the increased number of islet cells expressing PAX4 leads to the hypothesis that β-cells change to an earlier stage of differentiation or that novel β-cells are formed. Furthermore, the higher count of islet insulin/glucagon-positive cells might indicate that α-cells transform into β-cells or vice versa. Hence, reprogramming seems possible in diabetic cats, specifically in the islets.