Extra-pancreatic Source of Insulin in Chicken

Increasing prevalence of diabetes mellitus in the West, calls for tools to induce extra-pancreatic insulin production. In chickens, an extra-pancreatic insulin source has been suggested but never characterised. Here we show that the pancreas:adrenal ratios of basal insulin and somatostatin mRNA levels in chickens are over 100-fold lower than in humans, suggesting that the strict dominance of insulin synthesis in mammalian pancreatic islets is less pronounced in birds. Immunohistochemical signals of somatostatin were prominent in the pancreas and adrenal of chicken and quail but in rat, only in the pancreas. Insulin and somatostatin mRNA levels were induced in the adrenal 24 h after pancreatic anastomosis compared to a sham operation by ~10- and 40-fold, respectively (observed by both qPCR and RNA-seq analyses). The adrenal glands from operated chickens unlike those from sham operation stained positive with anti-insulin antibody. The RNA-seq-based comparison of the adrenals from operated and sham operated chickens revealed 2,870 differentially expressed protein-encoding genes, with typical pancreatic beta-cell transcripts UCN3, AGR2, CART and GDF15 being top upregulated. The most strongly induced gene pathways were insulin secretion and unfolded protein response—distinct beta-cell pathways. Yet, the trans-differentiation gene PDX1, was undetectable, seemingly replaced by upstream regulatory genes XBP1, CREB1/CREM , TGFB. This study suggests a new model system and new target genes for the study of enhanced insulin production outside of the pancreases.