5) We then investigated a long-acting analogue of ghrelin, relamorelin in combination with octreotide, the current first line treatment for these CHI patients. We demonstrate that the combination of these drugs act synergistically to increase blood glucose more than the sum of the individual drugs

4) In these mice, we tested ghrelin, which reversed the hypoglycaemia and reduced the human SC-islet specific insulin secretion

3) we then implanted immunocompromised mice with KCNJ11 wildtype and knockout SC-islets, demonstrating rapid development of hyperinsulinaemic hypoglycaemia in the mice implanted with the knockout SC-islets

2) We then tested insulin secretion affecting compounds in vitro for their ability to suppress the insulin hypersecretion from the KCNJ11 knockout SC-islets. We identified the expected reduction from the clinically used octreotide and exendin 9-39 with reduction with 3 novel compounds

1) We created KCNJ11 knockout stem cells, differentiated them to stem cell derived islets (SC-islets) and demonstrated over 3-fold increased insulin secretion in sub-stimulatory glucose, recapitulating the cardinal defect of congenital hyperinsulinism in vitro

Reporting on successful use of SC-islets in drug development for #congenitalhyperinsulinism! We identified ghrelin analogues as novel candidate drugs, demonstrating reversal of hypoglycaemia in mice, which was caused by the hyperinsulinaemic human SC-islets #PancSky www.biorxiv.org/content/10.1...