The prevalence of diabetes is increasing worldwide. Currently, pancreatic islet transplantation remains the only practical alternative for treatment of diabetes, although scarcity of available pancreas/islets remains a major limitation. There is a growing need to look for alternate sources of insulin producing cells.

We demonstrated for the first time that human gallbladder epithelium contains insulin-producing cells. Gallbladder, being next door neighbour to the pancreas shares several transcription factors during embryonic development. We isolated and characterized gallbladder epithelial cells for several pancreatic hormones (insulin, glucagon, somatostatin), transcription factors (Pdx1, Ngn3, MafA), epithelial and mesenchymal markers using multiple techniques including immunocytochemistry, flow cytometry, RNA-sequencing and real-time quantitative PCR (qPCR).
Freshly isolated gallbladder epithelial cells proliferate and undergo epithelial-to-mesenchymal transition (EMT) as demonstrated by lineage tracing, immuno-cytochemistry, time lapse imaging and qPCR.  Hes1, a negative regulator of Ngn3, is abundant in gallbladder epithelial cells and targeting the repression of Hes1 through small regulatory non-coding RNAs or dominant negative approaches can promote enhanced expression of pro-endocrine gene transcripts.
Functional studies involving in vitro stimulation as well as transplantation of gallbladder epithelium-derived insulin producing cells confirmed their potential for replacement therapy in diabetes.  Our studies demonstrate that human gallbladder epithelial cells produce, package and secrete insulin at a level that is higher than that achieved by most differentiated stem cells. We therefore believe that gallbladder cells have tremendous potential for cell replacement therapy in diabetes. A comparative profile of human gallbladder cells will be presented to understand the similarities in these cells with human pancreatic islets.