Alpha cells, the main source of IL-1ß in human pancreas.

ABSTRACT

Interleukin-1ß (IL-1ß) is known to trigger beta cell dysfunction in vitro and could potentially play a role during the pathogenesis of type 1 diabetes and type 2 diabetes. However, several clinical trials attempting to block IL-1ß function have had minimal success. We therefore re-investigated local expression of IL-1ß in human diabetic and non-diabetic pancreata. We obtained pancreatic tissue sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) including non-diabetic (n = 9), non-diabetic auto-antibody positive (AAb+, n = 5), type 1 diabetes (n = 6), and type 2 diabetes (n = 6) donors. Islets were systematically investigated for the presence of IL-1ß mRNA by in situ hybridization and IL-1ß protein by indirect immunofluorescence. We found that intra-islet IL-1ß was produced at comparable level in both non-diabetic and diabetic donors. Interestingly, the main source for IL-1ß was alpha cells but not beta cells. Our findings call into question the role of IL-1ß in the diabetic pancreas as it has been proposed in previous literature. Additionally, our results regarding the localization of IL-1ß should lead to further investigation into the role of IL-1ß in the physiology of pancreatic alpha cells.